A Polymorphism of a Platelet Glycoprotein Receptor as an Inherited Risk Factor for Coronary Thrombosis
Ethan J. Weiss, B.A., Paul F. Bray, M.D., Matthew Tayback, Sc.D., Steven P. Schulman, M.D., Thomas S. Kickler, M.D., Lewis C. Becker, M.D., James L. Weiss, M.D., Gary Gerstenblith, M.D., and Pascal J. Goldschmidt-Clermont, M.D.
Background Platelet glycoprotein IIb/IIIa is a membrane receptorfor fibrinogen and von Willebrand factor, and it has an importantrole in platelet aggregation. It is known to be involved inthe pathogenesis of acute coronary syndromes. Previously, wefound a high frequency of a particular polymorphism, PlA2, ofthe gene encoding glycoprotein IIIa in kindreds with a highprevalence of premature myocardial infarction.
Methods To investigate the relation between the PlA2polymorphismand acute coronary syndromes, we conducted a case–controlstudy of 71 case patients with myocardial infarction or unstableangina and 68 inpatient controls without known heart disease.The groups were matched for age, race, and sex. We used twomethods to determine the PlA genotype: reverse dot blot hybridizationand allele-specific restriction digestion.
Results The prevalence of PlA2 was 2.1 times higher among thecase patients than among the controls (39.4 percent vs. 19.1percent, P = 0.01). In a subgroup of patients whose diseasebegan before the age of 60 years, the prevalence of PlA2was50 percent, a value that was 3.6 times that among control subjectsunder 60 years of age (13.9 percent, P = 0.002). Among subjectswith the PlA2 polymorphism, the odds ratio for having a coronaryevent was 2.8 (95 percent confidence interval, 1.2 to 6.4).In the patients less than 60 years of age at the onset of disease,the odds ratio was 6.2 (95 percent confidence interval, 1.8to 22.4).
Conclusions We observed a strong association between the PlA2polymorphism of the glycoprotein IIIa gene and acute coronarythrombosis, and this association was strongest in patients whohad had coronary events before the age of 60 years.
Studies indicate that myocardial infarction and unstable anginaresult from the formation of a platelet aggregate at the siteof a ruptured coronary atherosclerotic plaque.1,2,3,4,5,6,7The formation of such aggregates requires the binding of fibrinogenand von Willebrand factor to the receptor, glycoprotein IIb/IIIa,on the platelet surface.6,8,9 Large trials have demonstrateda marked benefit of various inhibitors of platelet functionin both preventing and reducing the mortality and morbidityassociated with unstable coronary syndromes.10,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26Additional studies have linked ex vivo platelet reactivity tooutcome in patients after myocardial infarction.27 In sum, thereis strong evidence that platelets, and glycoprotein IIb/IIIain particular, have an important role in the pathogenesis ofacute coronary syndromes.
Platelet-membrane glycoproteins are highly polymorphic and canbe recognized as alloantigens or autoantigens.28 The alloimmunethrombocytopenias are due to the incompatibility of epitopeson the various platelet-surface glycoproteins.29 The alloantigenreferred to as PlA or Zw is the one most frequently implicatedin syndromes of immune-mediated platelet destruction.30,31 Kunickiand Aster demonstrated that anti-PlA1 antiserum from PlA1-negativepersons reacted with platelet glycoprotein IIIa.32 Subsequently,Newman et al. identified the molecular basis of this polymorphism:persons positive for PlA1 have a leucine at position 33 of matureglycoprotein IIIa; persons positive for PlA2 have a prolineat this position, which is the result of the substitution ofcytosine for thymidine at position 1565 in exon 2 of the glycoproteinIIIa gene.33 We recently determined the allelic frequenciesof PlA1 and PlA2 in several racial and ethnic groups in themetropolitan Baltimore area.34
Previously, we found an unexpectedly high frequency of familymembers homozygous for PlA2 in kindreds with a high prevalenceof acute coronary events at a relatively young age (under 60years).35 This observation led us to postulate that the presenceof at least one PlA2 allele may be related to the developmentof symptomatic unstable coronary heart disease. We conducteda case–control study to examine whether there was an associationbetween the PlA2 allele and unstable coronary syndromes, especiallyin persons less than 60 years of age.
Methods
Selection of Case Patients and Control Subjects
Studies on case patients and control subjects were approvedby the Joint Committee for Clinical Investigation of Johns HopkinsUniversity and Hospital. Genotypic analyses were performed on71 consecutive case patients admitted to the Coronary Care Unitof Johns Hopkins Hospital with an established diagnosis of myocardialinfarction or unstable angina as defined by World Health Organizationcriteria. Similar genotypic analyses were performed on controlsubjects matched with the case patients for age, race, and sex,but who had no documented history of either stable or unstableangina or myocardial infarction. The control subjects were selectedby reviewing patient charts from a population of patients admittedto the general medical and intensive care services of the hospital.We selected 68 consecutive subjects who fulfilled these criteria.
Demographic Characteristics
Demographic data were obtained on each subject from the officialmedical record at the time of enrollment and included the currentage (for control subjects), the age at the time of a first event(for case patients), sex, smoking history, blood pressure, totalserum cholesterol level, diabetes status, and history of coronaryevents. Because the prevalence of the PlA2 allele is known tobe lower among blacks than among whites, we limited the studyto the white population.34,36
Determination of PlA Genotypes
Genomic DNA was isolated from 200 µl of whole blood aspreviously described or with the QIAamp blood kit (Qiagen, Chatsworth,Calif.).37 To detect the substitution of cytosine for thymidineresponsible for the PlA2 polymorphism at position 1565 in exon2 of the glycoprotein IIIa gene, we used both reverse dot blothybridization and allele-specific restriction digestion (exonnumbering and nucleotide sequence are from Zimrin et al.38).Exon 2 was amplified from genomic DNA from case patients orcontrols in a polymerase chain reaction (PCR) with primers flankingthe exon, as previously described.39 For the reverse dot blothybridization reaction, oligonucleotides specific for eitherthe PlA1 or PlA2 allele were covalently attached to filtersand hybridized with biotinylated PCR products of glycoproteinIIIa exon 2, and reactivity was assessed by an enhanced chemiluminescencetechnique, as described previously.34,37 These allele-specifichybridization data were confirmed with restriction-enzyme digestionwith MspI and NciI (New England Biolabs, Beverly, Mass.), whichare able to distinguish the PlA1 allele from the PlA2 allelebecause new restriction sites are generated as the result ofthe PlA2 polymorphism. Exon 2 PCR products were digested separatelywith both enzymes, and the resulting fragments were analyzedon a 3 percent agarose gel. The results of both techniques wereconfirmed by at least two independent investigators who wereunaware of the origin of the DNA.
Statistical Analysis
The size of the sample was established after pilot studies indicatedthat the prevalence of PlA2 among the case patients would beapproximately 40 percent and the expected prevalence in controlsubjects would not exceed 20 percent. With the expectation thata difference of this magnitude would strongly support the conceptthat PlA2 is a significant genetic risk factor, and with a one-sidedalpha error of 0.05, the size of the sample was set at 71 tolimit the beta error to 0.1. Student's t-test was used to compareestablished risk factors for coronary heart disease in the casepatients and the control subjects, with a two-tailed test usedfor the continuous variables. A P value of 0.05 or less wasconsidered to indicate statistical significance. Discrete data(including data on the PlA alleles) were analyzed by the chi-squaretest. The strength of the association of the PlA2 genetic factorwith the occurrence of acute coronary events was estimated bycalculation of the odds ratios with EpiInfo software (version6, Centers for Disease Control and Prevention, Atlanta) andthe Cornfield method for the calculation of 95 percent confidenceintervals. The relative strength of association of other riskfactors was measured in a similar manner. The significance ofthe difference in the odds ratios was not tested, since thesample size was not designed for such analyses. The relationof the PlA allele to each of the remaining predictor variableswas examined by bivariate chi-square analysis. Finally, theassociation of the PlA2 allele with coronary events, standardizedfor the other risk factors, was determined by the multiple logistic-regressionmethod with the Stata statistical package (version 4.0, Stata,College Station, Tex.).
Results
Characteristics of the Study Population
Table 1 shows the prevalence of selected risk factors for coronaryheart disease among the case patients and controls. The twogroups were matched according to age, race, and sex, and therewere therefore no significant differences in these variables.Owing to the sample size, the only risk factor that differedsignificantly between the groups was smoking status (P = 0.05).
Table 1. Prevalence of Selected Risk Factors for Coronary Heart Disease among Case Patients and Controls.
Prevalence of PlA2
Genotyping results for 3 of the 71 case patients are shown inFigure 1A, Figure 1B, and Figure 1C, demonstrating the threepossible PlA allelic combinations. Table 2 summarizes the genotypingdata for all case patients and controls. The prevalence of PlA2among the case subjects was 39.4 percent (percentage of subjectswho were either heterozygous [PlA1/PlA2] or homozygous [PlA2/PlA2]),a value that was significantly higher than the prevalence amongthe 68 controls (19.1 percent, P = 0.01). The association betweenPlA2 and coronary events was even stronger in patients who wereless than 60 years of age when they had their first coronaryevent. Of the 42 such patients, 50 percent carried at leastone PlA2 allele, as compared with 13.9 percent of the 36 controlswho were less than 60 years of age (P = 0.002).
Figure 1. Genotyping of PlA Loci by Allele-Specific Restriction Digestion and Re-verse Dot Blot Hybridization.
Panel A shows the restriction map of exon 2 of the glycoprotein IIIa gene, undigested fragments, and fragments resulting when PlA1 or PlA2 PCR products were digested with the restriction enzymes MspI and Nci I. Sizes (in base pairs) are indicated below the horizontal lines. The vertical bars indicate the ends of PCR fragments or digestion products. For clarity and because it does not cause a detectable change in the fragment sizes, an additional MspI site (present in both PlA alleles) 7 bp from the 3' MspI site is not shown. Panel B shows a representative ethidium-stained 3 percent agarose gel containing undigested PCR products (lanes 1, 5, and 8) and PCR products digested with MspI (lanes 2, 6, and 9) and Nci I (lanes 3, 7, and 10) corresponding to the three possible allelic combinations: PlA1/PlA1(lanes 1, 2, and 3), PlA1/PlA2(lanes 5, 6, and 7), and PlA2/PlA2 (lanes 8, 9, and 10). Lane 4 shows X174 DNA cut with HaeIII, which was used as a size marker. Panel C shows the results of reverse dot blot hybridization with the DNA shown in Panel B. Filters are shown with PlA1-allele–specific oligonucleotides at the top and PlA2-allele–specific oligonucleotides at the bottom.
Table 2. Genotypes of the Case Patients and Controls According to Age.
Comparison of Major Risk Factors for Coronary Heart Disease
Among the major risk factors for coronary heart disease examinedin this study, the risk factor associated with the highest estimatedodds ratio was carriage of the PlA2 allele (odds ratio, 2.8;95 percent confidence interval, 1.2 to 6.4), followed in orderby smoking (odds ratio, 2.2; 95 percent confidence interval,1.0 to 4.8), hypertension (systolic blood pressure, >140mm Hg) (odds ratio, 1.9; 95 percent confidence interval, 0.9to 3.9), and hypercholesterolemia (total serum cholesterol level,>200 mg per deciliter [5.2 mmol per liter]) (odds ratio,1.3; 95 percent confidence interval, 0.5 to 3.0) (Table 3).The prevalence of diabetes mellitus was similarly high amongcase patients and control subjects. As anticipated, the oddsratios for each of the risk factors, including PlA2, were higherin the subgroup of case patients less than 60 years of age thanin controls less than 60 years of age. In this subgroup, therisk factor associated with the highest estimated odds ratiowas again the PlA2 allele (odds ratio, 6.2; 95 percent confidenceinterval, 1.8 to 22.4), followed in order by smoking (odds ratio,3.8; 95 percent confidence interval, 1.2 to 12.0), hypercholesterolemia(odds ratio, 3.7; 95 percent confidence interval, 0.8 to 18.7),and hypertension (odds ratio, 2.1; 95 percent confidence interval,0.7 to 5.9) (Table 3).
Table 3. Odds Ratios for Selected Risk Factors, According to Age.
A multiple logistic-regression model that adjusted for the presenceof smoking, hypertension, hypercholesterolemia, and an age greaterthan 60 years provided an odds ratio of 3.3 (95 percent confidenceinterval, 1.4 to 7.7) for the relation between acute coronaryevents and the PlA2 allele. This was consistent with the findingthat the bivariate association of the allele with smoking, hypertension,hypercholesterolemia, and an age greater than 60 years was uniformlynot statistically significant (data not shown).
Discussion
Our data demonstrate an association between the PlA2 polymorphismof glycoprotein IIIa and the occurrence of acute coronary thrombosis.We found a significantly higher prevalence of subjects withat least one PlA2 allele among those with either myocardialinfarction or unstable angina than among a control group matchedfor sex, age, and race. If this polymorphism represents an inheritedrisk factor for myocardial infarction or unstable angina, onewould predict an even higher prevalence of this risk factoramong persons in whom these disorders occur at a younger age(before the age of 60 years), and this is what we found.
Data from northern and central Europe estimate the phenotypicfrequency and genotypic frequency of PlA2 to be 26.5 percentand 15 percent, respectively.40 These estimates were derivedfrom studying subjects whose genetic background may differ fromthat of our subjects. In our previous work, we determined thatthe prevalence of PlA2 among 100 white subjects from the Baltimorearea was 20 percent (genotypic frequency, 11 percent).34 Ascompared with the subjects in the European studies, the controlsubjects in the current study had a slightly lower prevalenceof PlA2 (19.1 percent vs. 26.5 percent), but one that was virtuallyidentical to the prevalence in our previous study in Baltimore.Between our two studies we have performed genotyping on 336chromosomes from white control subjects, and the results providevery strong evidence that the prevalence of PlA2 among thesesubjects in the metropolitan Baltimore area is approximately20 percent. For this reason, we believe the data on controlsubjects in the current study accurately reflect the populationgenetics in our geographic area and that this group is a validone to use for comparison with our case patients.
Finally, although variation in the genetic background is themost likely explanation for differences in the prevalence ofthe PlA2 phenotype between the United States and Europe, theearlier studies of European populations used immunophenotyping,which is less specific than genotyping.
To assess the association between PlA2 and acute coronary events,we compared the risk of having a coronary event associated withthe PlA2 polymorphism with that associated with four major cardiacrisk factors. Among the major risk factors tested, the one associatedwith the largest odds ratio of having a coronary event, bothfor the entire group and for the subgroup of younger patients(age less than 60 years at first acute coronary event), wasthe PlA2 allele (Table 3). In addition, we conducted a multiplelogistic-regression analysis adjusting for the presence of smoking,hypertension, hypercholesterolemia, and an age greater than60 years, which demonstrated an independent association betweenPlA2 and acute coronary events. All the risk factors testedyielded odds ratios consistent with what one would expect fora major risk factor for coronary heart disease, except for diabetes.However, we believe that the low odds ratio associated withdiabetes is a result of the selection of control subjects froma population of inpatients with a high prevalence of diabetes.
One theoretical explanation for the increased prevalence ofPlA2 among the case patients could be a higher survival rateafter myocardial infarction in this group than in PlA2-negativepatients. However, if PlA2 did provide a survival advantage,the prevalence of PlA2 would be unlikely to be increased amongthe case patients in whom disease occurred before the age of60 years. Instead, our hypothesis is that PlA2 is a risk factorfor coronary heart disease events, particularly among youngerpersons. In fact, among the case patients, there was a significantdifference of more than 7 years in the age at onset of diseasebetween the PlA2-positive patients and the PlA2-negative patients(51.8 vs. 59.2 years, P = 0.02).
In addition to our findings related to the prognostic potentialof PlA2, our results could directly affect the treatment ofacute coronary events. For example, although aspirin has beenthe platelet inhibitor of choice for the treatment of unstablecoronary syndromes, recent studies indicate that treatment withspecific inhibitors of glycoprotein IIb/IIIa leads to betteroutcomes than does aspirin therapy.23,24,25,26,41 It is conceivablethat PlA2-positive patients would receive extra benefit fromdirect therapy with anti–glycoprotein IIb/IIIa, providinga rationale for decisions regarding the choice of antiplatelettherapy for patients with unstable coronary syndromes.41
Supported by grants from the National Institutes of Health (HL49762and NR02241), a grant from the Rebecca and Bernard Bernard Foundation,the Ciccarone Center for the Prevention of Heart Disease, andthe Rogers–Wilbur Foundation. Dr. Goldschmidt-Clermontis an Established Investigator of the American Heart Association.
We are indebted to the members of Kindred PT1 for their invaluablecontribution to this study; to Hyun Kim, Emily E. Milliken,Ying Jin, William S. Shear, and Lindsay D. Coleman for excellenttechnical support; to Dr. Pamela Ouyang, Lydia Nelson, and membersof the medical house staff and nursing staff of Johns HopkinsHospital for assistance in the recruitment of patients and theprocurement of blood samples; to Drs. Kenneth L. Baughman andRoger Blumenthal for providing medical records and scientificexpertise; and to Dr. Paul M. Ridker for thoughtful discussions.
Source Information
From the Department of Medicine, Divisions of Cardiology (E.J.W., S.P.S., L.C.B., J.L.W., G.G., P.J.G.-C.) and Hematology (E.J.W., P.F.B., T.S.K.), the Department of Pathology (P.F.B., T.S.K.), and the Department of Cell Biology and Anatomy (P.J.G.-C.), Johns Hopkins University School of Medicine; and Johns Hopkins University School of Hygiene and Public Health (M.T.) — both in Baltimore.
Address reprint requests to Dr. Goldschmidt-Clermont at Bernard Laboratory, Ross 1023, Johns Hopkins Medical School, 720 Rutland Ave., Baltimore, MD 21205.
References
Chandler AB, Chapman I, Erhardt LR, et al. Coronary thrombosis in myocardial infarction: report of a workshop on the role of coronary thrombosis in the pathogenesis of acute myocardial infarction. Am J Cardiol 1974;34:823-833. [CrossRef][Medline]
Lam JYT, Chesebro JH, Steele PM, Dewanjee MK, Badimon L, Fuster V. Deep arterial injury during experimental angioplasty: relation to a positive indium-111-labeled platelet scintigram, quantitative platelet deposition and mural thrombosis. J Am Coll Cardiol 1986;8:1380-1386. [Abstract]
Fitzgerald DJ, Roy L, Catella F, FitzGerald GA. Platelet activation in unstable coronary artery disease. N Engl J Med 1986;315:983-989. [Abstract]
Davies MJ. A macro and micro view of coronary vascular insult in ischemic heart disease. Circulation 1990;82:Suppl:II-38.
Fuster V, Badimon L, Badimon JJ, Chesebro JH. The pathogenesis of coronary artery disease and the acute coronary syndromes. N Engl J Med 1992;326:242-250. [Medline]
Jang Y, Lincoff AM, Plow EF, Topol EJ. Cell adhesion molecules in coronary artery disease. J Am Coll Cardiol 1994;24:1591-1601. [Abstract]
DeWood MA, Stifter WF, Simpson CS, et al. Coronary arteriographic findings soon after non-q-wave myocardial infarction. N Engl J Med 1986;315:417-423. [Abstract]
Plow EF, Ginsberg MH. Cellular adhesion: GPIIb-IIIa as a prototypic adhesion receptor. Prog Hemost Thromb 1989;9:117-156. [Medline]
Coller BS. Platelets and thrombolytic therapy. N Engl J Med 1990;322:33-42. [Medline]
Lewis HD Jr, Davis JW, Archibald DG, et al. Protective effects of aspirin against acute myocardial infarction and death in men with unstable angina: results of a Veterans Administration Cooperative study. N Engl J Med 1983;309:396-403. [Abstract]
Cairns JA, Gent M, Singer J, et al. Aspirin, sulfinpyrazone, or both in unstable angina: results of a Canadian Multicenter Trial. N Engl J Med 1985;313:1369-1375. [Abstract]
ISIS-2 (Second International Study of Infarct Survival) Collaborative Group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17 187 cases of suspected acute myocardial infarction: ISIS-2. Lancet 1988;2:349-360. [Medline]
Ridker PM, Manson JE, Buring JE, Muller JE, Hennekens CH. Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians. Circulation 1990;82:897-902. [Free Full Text]
Ridker PM, Manson JE, Gaziano JM, Buring JE, Hennekens CH. Low-dose aspirin therapy for chronic stable angina: a randomized, placebo-controlled clinical trial. Ann Intern Med 1991;114:835-839.
Ridker PM, Manson JE, Buring JE, Goldhaber SZ, Hennekens CH. Clinical characteristics of nonfatal myocardial infarction among individuals on prophylactic low-dose aspirin therapy. Circulation 1991;84:708-711. [Free Full Text]
Verheut FW, van der Laarse A, Funke-Kupper AJ, Sterkman LG, Galema TW, Roos JP. Effects of early intervention with low-dose aspirin (100 mg) on infarct size, reinfarction and mortality in anterior wall acute myocardial infarction. Am J Cardiol 1990;66:267-270. [CrossRef][Medline]
The RISC Group. Risk of myocardial infarction and death during treatment with low dose aspirin and intravenous heparin in men with unstable coronary artery disease. Lancet 1990;336:827-830. [CrossRef][Medline]
Nyman I, Larsson H, Wallentin L. Prevention of serious cardiac events by low-dose aspirin in patients with silent myocardial ischemia: the Research Group on Instability in Coronary Artery Disease in Southeast Sweden. Lancet 1992;340:497-501. [CrossRef][Medline]
Juul-Moller S, Edvardsson N, Jahnmatz B, Rosen A, Sorenson S, Omblus R. Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris: the Swedish Angina Pectoris Aspirin Trial (SAPAT) Group. Lancet 1992;340:1421-1425. [CrossRef][Medline]
Hoffman W, Förster W. Two year Cottbus reinfarction study with 30 mg aspirin per day. Prostaglandins Leukot Essent Fatty Acids 1991;44:159-169. [CrossRef][Medline]
The Persantine-Aspirin Reinfarction Study Research Group. Persantine and aspirin in coronary heart disease. Circulation 1980;62:449-461. [Free Full Text]
Klimt CR, Knatterud GL, Stamler J, Meier P. Persantine-Aspirin Reinfarction Study. II. Secondary coronary prevention with persantine and aspirin. J Am Coll Cardiol 1986;7:251-269. [Abstract]
Gold HK, Gimple LW, Yasuda T, et al. Pharmacodynamic study of F(ab')2 fragments of murine monoclonal antibody 7E3 directed against human platelet glycoprotein IIb/IIIa in patients with unstable angina pectoris. J Clin Invest 1990;86:651-659.
Coller BS. Blockade of platelet GPIIb/IIIa receptors as an antithrombotic strategy. Circulation 1995;92:2373-2380. [Free Full Text]
Mickelson JK, Simpson PJ, Lucchesi BR. Antiplatelet monoclonal F(ab')2 antibody directed against the platelet GPIIb/IIIa receptor complex prevents coronary artery thrombosis in the canine heart. J Mol Cell Cardiol 1989;21:393-405. [CrossRef][Medline]
The EPIC Investigators. Use of a monoclonal antibody directed against the platelet glycoprotein IIb/IIIa receptor in high-risk coronary angioplasty. N Engl J Med 1994;330:956-961. [Free Full Text]
Trip MD, Cats VM, van Capelle FJL, Vreeken J. Platelet hyperreactivity and prognosis in survivors of myocardial infarction. N Engl J Med 1990;322:1549-1554. [Abstract]
Kickler TS. Platelet immunology. In: Anderson KC, Ness PM, eds. Scientific basis of transfusion medicine: implications for clinical practice. Philadelphia: W.B. Saunders, 1994:304-15.
Shulman NR, Aster RH, Leitner A, Hiller MC. Immunoreactions involving platelets. V. Post-transfusion purpura due to a complement-fixing antibody against a genetically controlled platelet antigen: a proposed mechanism for thrombocytopenia and its relevance in "autoimmunity." J Clin Invest 1961;40:1597-1620. [Medline]
van Loghem JJ Jr, Dorfmeijer H, van der Hart M, Schreuder F. Serological and genetical studies on a platelet antigen (Zw). Vox Sang 1959;4:161-169. [Medline]
Kunicki TJ, Aster RH. Isolation and immunologic characterization of the human platelet alloantigen, PlA1. Mol Immunol 1979;16:353-360. [CrossRef][Medline]
Newman PJ, Derbes RS, Aster RH. The human platelet alloantigens, PlA1 and PlA2, are associated with a leucine33/proline33 amino acid polymorphism in membrane glycoprotein IIIa, and are distinguishable by DNA typing. J Clin Invest 1989;83:1778-1781.
Kim HO, Jin Y, Kickler TS, Blakemore K, Kwon OH, Bray PF. Gene frequencies of the five major human platelet antigens in African American, white, and Korean populations. Transfusion 1995;35:863-867. [CrossRef][Medline]
Weiss EJ, Goldschmidt-Clermont PJ, Grigoryev D, Jin Y, Kickler TS, Bray PF. A monoclonal antibody (SZ21) specific for platelet GPIIIa distinguishes PlA1 from PlA2. Tissue Antigens 1995;46:374-381. [Medline]
Ramsey G, Salamon DJ. Frequency of PLA1 in blacks. Transfusion 1986;26:531-532. [Medline]
Bray PF, Jin Y, Kickler T. Rapid genotyping of the five major platelet alloantigens by reverse dot-blot hybridization. Blood 1994;84:4361-4367. [Free Full Text]
Zimrin AB, Gidwitz S, Lord S, et al. The genomic organization of platelet glycoprotein IIIa. J Biol Chem 1990;265:8590-8595. [Free Full Text]
Jin Y, Dietz HC, Nurden A, Bray PF. Single-strand conformation polymorphism analysis is a rapid and effective method for the identification of mutations and polymorphisms in the gene for glycoprotein IIIa. Blood 1993;82:2281-2288. [Free Full Text]
von dem Borne AEG, Decary F. Nomenclature of platelet-specific antigens. Transfusion 1990;30:477-477.
Lefkovits J, Plow EF, Topol EJ. Platelet glycoprotein IIb/IIIa receptors in cardiovascular medicine. N Engl J Med 1995;332:1553-1559. [Free Full Text]
Lambrinoudaki, I., Kaparos, G., Papadimitriou, D., Sergentanis, T. N, Creatsa, M., Alexandrou, A., Logothetis, E., Christodoulakos, G., Kouskouni, E
(2008). Methylenetetrahydrofolate reductase C677T polymorphism is associated with central adiposity and increased androgenicity in healthy postmenopausal women. Eur J Endocrinol
159: 233-241
[Abstract][Full Text]
Medina, P., Navarro, S., Corral, J., Zorio, E., Roldan, V., Estelles, A., Santamaria, A., Marin, F., Rueda, J., Bertina, R. M., Espana, F., for the RECAVA Thrombosis Groups,
(2008). Endothelial protein C receptor polymorphisms and risk of myocardial infarction. haematol
93: 1358-1363
[Abstract][Full Text]
Jimenez, S, Tassies, D, Espinosa, G, Garcia-Criado, A, Plaza, J, Monteagudo, J, Cervera, R, Reverter, J C
(2008). Double heterozygosity polymorphisms for platelet glycoproteins Ia/IIa and IIb/IIIa increases arterial thrombosis and arteriosclerosis in patients with the antiphospholipid syndrome or with systemic lupus erythematosus. Ann Rheum Dis
67: 835-840
[Abstract][Full Text]
Chandrakantan, A., McDermott, D. H., Bich Tran, H. T., Jurewicz, M., Gallon, L., Gaston, R., Milford, E., Abdi, R.
(2007). Role of {beta}3 Integrin in Acute Renal Allograft Rejection in Humans. CJASN
2: 1268-1273
[Abstract][Full Text]
Momary, K. M.
(2007). Cardiovascular Pharmacogenomics. Journal of Pharmacy Practice
20: 265-276
[Abstract]
Wierman, M. E., Kohrt, W. M.
(2007). Review Article: Vascular and Metabolic Effects of Sex Steroids: New Insights Into Clinical Trials. Reproductive Sciences
14: 300-314
[Abstract]
Ostojic, L., Zelenika, D., Zotz, R.B., Sucker, C., Ostojic, Z., Loncar, R.
(2007). Platelet Receptor HPA-1 Polymorphism of {alpha}IIb{beta}3 and 807 C/T Polymorphism of {alpha}2{beta}1 and Buerger's Disease. ANGIOLOGY
58: 169-174
[Abstract]
Undas, A., Brummel-Ziedins, K. E., Mann, K. G.
(2007). Antithrombotic properties of aspirin and resistance to aspirin: beyond strictly antiplatelet actions. Blood
109: 2285-2292
[Abstract][Full Text]
Berge, E., Haug, K. B. F., Charlotte Sandset, E., Kristine Haugbro, K., Turkovic, M., Sandset, P. M.
(2007). The Factor V Leiden, Prothrombin Gene 20210GA, Methylenetetrahydrofolate Reductase 677CT and Platelet Glycoprotein IIIa 1565TC Mutations in Patients With Acute Ischemic Stroke and Atrial Fibrillation. Stroke
38: 1069-1071
[Abstract][Full Text]
Lim, E., Carballo, S., Cornelissen, J., Ali, Z. A., Grignani, R., Bellm, S., Large, S.
(2007). Dose-Related Efficacy of Aspirin After Coronary Surgery in Patients With PlA2 Polymorphism (NCT00262275). Ann. Thorac. Surg.
83: 134-138
[Abstract][Full Text]
Oksala, N. K.J., Heikkinen, M., Mikkelsson, J., Pohjasvaara, T., Kaste, M., Erkinjuntti, T., Karhunen, P. J.
(2007). Smoking and the Platelet Fibrinogen Receptor Glycoprotein IIb/IIIA PlA1/A2 Polymorphism Interact in the Risk of Lacunar Stroke and Midterm Survival. Stroke
38: 50-55
[Abstract][Full Text]
Ndrepepa, G., Kastrati, A., Mehilli, J., Neumann, F.-J., ten Berg, J., Bruskina, O., Dotzer, F., Seyfarth, M., Pache, J., Dirschinger, J., Ulm, K., Berger, P. B., Schomig, A.
(2006). Age-Dependent Effect of Abciximab in Patients With Acute Coronary Syndromes Treated With Percutaneous Coronary Interventions. Circulation
114: 2040-2046
[Abstract][Full Text]
Lasne, D., Jude, B., Susen, S.
(2006). From normal to pathological hemostasis: [De l'hemostase normale a l'hemostase pathologique].. Canadian J. Anesthesia
53: S2-S11
[Abstract][Full Text]
Mathew, J. P., Rinder, H. M., Smith, B. R., Newman, M. F., Rinder, C. S.
(2006). Transcerebral Platelet Activation After Aortic Cross-Clamp Release is Linked to Neurocognitive Decline.. Ann. Thorac. Surg.
81: 1644-1649
[Abstract][Full Text]
Vijayan, K. V., Bray, P. F.
(2006). Molecular Mechanisms of Prothrombotic Risk Due to Genetic Variations in Platelet Genes: Enhanced Outside-In Signaling Through the Pro33 Variant of Integrin {beta}3.. Exp. Biol. Med.
231: 505-513
[Abstract][Full Text]
Koh, K. K., Yoon, B.-K.
(2006). Controversies regarding hormone therapy: Insights from inflammation and hemostasis. Cardiovasc Res
70: 22-30
[Abstract][Full Text]
Kubisz, P., Ivankova, J., Holly, P., Stasko, J., Musia/l, J.
(2006). The Glycoprotein IIIa PLA1/A2 Polymorphism--A Defect Responsible for the Sticky Platelet Syndrome?. CLIN APPL THROMB HEMOST
12: 117-119
Podgoreanu, M. V., Schwinn, D. A.
(2005). New Paradigms in Cardiovascular Medicine: Emerging Technologies and Practices: Perioperative Genomics. J Am Coll Cardiol
46: 1965-1977
[Abstract][Full Text]
Yee, D. L., Sun, C. W., Bergeron, A. L., Dong, J.-f., Bray, P. F.
(2005). Aggregometry detects platelet hyperreactivity in healthy individuals. Blood
106: 2723-2729
[Abstract][Full Text]
Papp, E., Havasi, V., Bene, J., Komlosi, K., Czopf, L., Magyar, E., Feher, C., Feher, G., Horvath, B., Marton, Z., Alexy, T., Habon, T., Szabo, L., Toth, K., Melegh, B.
(2005). Glycoprotein IIIA Gene (PlA) Polymorphism and Aspirin Resistance: Is There Any Correlation?. The Annals of Pharmacotherapy
39: 1013-1018
[Abstract][Full Text]
MacCallum, P. K.
(2005). Markers of Hemostasis and Systemic Inflammation in Heart Disease and Atherosclerosis in Smokers. Proc Am Thorac Soc
2: 34-43
[Abstract][Full Text]
Amit, G., Yermiyahu, T., Gilutz, H., Ilia, R., Zahger, D.
(2005). Thrombocytopenia, Immunoglobulin Treatment, and Acute Myocardial Infarction: A Case Report. ANGIOLOGY
56: 229-231
[Abstract]
Ginsburg, D.
(2005). Genetic Risk Factors for Arterial Thrombosis and Inflammation. ASH Education Book
2005: 442-444
[Abstract][Full Text]
Samaha, F. F., Hibbard, C., Sacks, J., Chen, H., Varello, M. A., George, T., Kahn, M. L.
(2004). Measurement of Platelet Collagen Receptor Density in Human Subjects. Arterioscler. Thromb. Vasc. Bio.
24: e181-e182
[Full Text]
Schulman, S. P.
(2004). Antiplatelet Therapy in Non-ST-Segment Elevation Acute Coronary Syndromes. JAMA
292: 1875-1882
[Abstract][Full Text]
Iniesta, J. A., Gonzalez-Conejero, R., Piqueras, C., Vicente, V., Corral, J.
(2004). Platelet GP IIIa Polymorphism HPA-1 (PlA) Protects Against Subarachnoid Hemorrhage. Stroke
35: 2282-2286
[Abstract][Full Text]
Xiong, J.-P., Stehle, T., Goodman, S. L., Arnaout, M. A.
(2004). A Novel Adaptation of the Integrin PSI Domain Revealed from Its Crystal Structure. J. Biol. Chem.
279: 40252-40254
[Abstract][Full Text]
Houel, R., Mazoyer, E., Boval, B., Kirsch, M., Vermes, E., Drouet, L., Loisance, D. Y.
(2004). Platelet activation and aggregation profile in prolonged external ventricular support. J. Thorac. Cardiovasc. Surg.
128: 197-202
[Abstract][Full Text]
Koh, K. K., Sakuma, I.
(2004). Should Progestins Be Blamed for the Failure of Hormone Replacement Therapy to Reduce Cardiovascular Events in Randomized Controlled Trials?. Arterioscler. Thromb. Vasc. Bio.
24: 1171-1179
[Abstract][Full Text]
Slowik, A., Dziedzic, T., Turaj, W., Pera, J., Glodzik-Sobanska, L., Szermer, P., Malecki, M. T., Figlewicz, D. A., Szczudlik, A.
(2004). A2 Alelle of GpIIIa Gene Is a Risk Factor for Stroke Caused by Large-Vessel Disease in Males. Stroke
35: 1589-1593
[Abstract][Full Text]
Narizhneva, N. V., Byers-Ward, V. J., Quinn, M. J., Zidar, F. J., Plow, E. F., Topol, E. J., Byzova, T. V.
(2004). Molecular and Functional Differences Induced in Thrombospondin-1 by the Single Nucleotide Polymorphism Associated with the Risk of Premature, Familial Myocardial Infarction. J. Biol. Chem.
279: 21651-21657
[Abstract][Full Text]
Eriksson, A.-L., Skrtic, S., Niklason, A., Hulten, L. M., Wiklund, O., Hedner, T., Ohlsson, C.
(2004). Association between the low activity genotype of catechol-O-methyltransferase and myocardial infarction in a hypertensive population. Eur Heart J
25: 386-391
[Abstract][Full Text]
Potapov, E. V., Ignatenko, S., Nasseri, B. A., Loebe, M., Harke, C., Bettmann, M., Doller, A., Regitz-Zagrosek, V., Hetzer, R.
(2004). Clinical significance of PlA polymorphism of platelet GP IIb/IIIa receptors during long-term VAD support. Ann. Thorac. Surg.
77: 869-874
[Abstract][Full Text]
Voetsch, B., Loscalzo, J.
(2004). Genetic Determinants of Arterial Thrombosis. Arterioscler. Thromb. Vasc. Bio.
24: 216-229
[Abstract][Full Text]
Macchi, L., Christiaens, L., Brabant, S., Sorel, N., Ragot, S., Allal, J., Mauco, G., Brizard, A.
(2003). Resistance in vitro to low-dose aspirin is associated with platelet PlA1 (GP IIIa) polymorphism but not with C807T(GP Ia/IIa) and C-5T kozak (GP Ib{alpha}) polymorphisms. J Am Coll Cardiol
42: 1115-1119
[Abstract][Full Text]
Bojesen, S. E., Juul, K., Schnohr, P., Tybjaerg-Hansen, A., Nordestgaard, B.o. G.
(2003). Platelet glycoprotein IIb/IIIa PlA2/PlA2 homozygosity associated with risk of ischemic cardiovascular disease and myocardial infarction in young men: The Copenhagen City Heart Study. J Am Coll Cardiol
42: 661-667
[Abstract][Full Text]
Tolusso, B, Fabris, M, Gremese, E, Mosca, M, Rovere-Querini, P, Ferraccioli, G F
(2003). Platelet GPIIb/IIIa (P1A1/2) polymorphism in SLE: clinical and laboratory association. Ann Rheum Dis
62: 781-782
[Full Text]
Atherosclerosis, Thrombosis, and Vascular Biology,
(2003). No Evidence of Association Between Prothrombotic Gene Polymorphisms and the Development of Acute Myocardial Infarction at a Young Age. Circulation
107: 1117-1122
[Abstract][Full Text]
Pontiggia, L., Lassila, R., Pederiva, S., Schmid, H.-R., Burger, M., Beer, J. H.
(2002). Increased Platelet-Collagen Interaction Associated With Double Homozygosity for Receptor Polymorphisms of Platelet GPIa and GPIIIa. Arterioscler. Thromb. Vasc. Bio.
22: 2093-2098
[Abstract][Full Text]
Leebeek, F.W.G., Boersma, E., Cannon, C.P., van de Werf, F.J.J., Simoons, M.L.
(2002). Oral glycoprotein IIb/IIIa receptor inhibitors in patients with cardiovascular disease: why were the results so unfavourable. Eur Heart J
23: 444-457
[Full Text]
Braunstein, J. B., Kershner, D. W., Bray, P., Gerstenblith, G., Schulman, S. P., Post, W. S., Blumenthal, R. S.
(2002). Interaction of Hemostatic Genetics With Hormone Therapy : New Insights To Explain Arterial Thrombosis in Postmenopausal Women. Chest
121: 906-920
[Abstract][Full Text]
Benze, G., Heinrich, J., Schulte, H., Rust, S., Nowak-Gottl, U., Tataru, M.-C., Kohler, E., Assmann, G., Junker, R.
(2002). Association of the GPIa C807T and GPIIIa PlA1/A2 polymorphisms with premature myocardial infarction in men. Eur Heart J
23: 325-330
[Abstract][Full Text]
Herrington, D. M., Klein, K. P.
(2001). Genome and Hormones: Gender Differences in Physiology: Invited Review: Pharmacogenetics of estrogen replacement therapy. J. Appl. Physiol.
91: 2776-2784
[Abstract][Full Text]
O'Connor, F. F., Shields, D. C., Fitzgerald, A., Cannon, C. P., Braunwald, E., Fitzgerald, D. J.
(2001). Genetic variation in glycoprotein IIb/IIIa (GPIIb/IIIa) as a determinant of the responses to an oral GPIIb/IIIa antagonist in patients with unstable coronary syndromes. Blood
98: 3256-3260
[Abstract][Full Text]
Undas, A., Brummel, K., Musial, J., Mann, K. G., Szczeklik, A.
(2001). PlA2 Polymorphism of {beta}3 Integrins Is Associated With Enhanced Thrombin Generation and Impaired Antithrombotic Action of Aspirin at the Site of Microvascular Injury. Circulation
104: 2666-2672
[Abstract][Full Text]
Barakat, K., Kennon, S., Hitman, G. A., Aganna, E., Price, C. P., Mills, P. G., Ranjadayalan, K., North, B., Clarke, H., Timmis, A. D.
(2001). Interaction between smoking and the glycoprotein IIIa P1A2 polymorphism in Non-ST-elevation acute coronary syndromes. J Am Coll Cardiol
38: 1639-1643
[Abstract][Full Text]
Cadroy, Y., Sakariassen, K. S., Charlet, J.-P., Thalamas, C., Boneu, B., Sie, P.
(2001). Role of 4 platelet membrane glycoprotein polymorphisms on experimental arterial thrombus formation in men. Blood
98: 3159-3161
[Abstract][Full Text]
Agema, W. R. P., Jukema, J. W., Pimstone, S. N., Kastelein, J. J. P.
(2001). Genetic aspects of restenosis after percutaneous coronary interventions;towards more tailored therapy. Eur Heart J
22: 2058-2074
O'Shaughnessy, K. M, Fu, B., Downing, S., Morris, N. H
(2001). Thrombophilic polymorphisms in pre-eclampsia: altered frequency of the functional 98C>T polymorphism of glycoprotein IIIa. J. Med. Genet.
38: 775-777
[Full Text]
Kandzari, D. E., Goldschmidt-Clermont, P. J.
(2001). Platelet polymorphisms and ischemic heart disease: moving beyond traditional risk factors. J Am Coll Cardiol
38: 1028-1032
[Full Text]
Hessner, M. J., Dinauer, D. M., Kwiatkowski, R., Neri, B., Raife, T. J.
(2001). Age-dependent Prevalence of Vascular Disease-associated Polymorphisms among 2689 Volunteer Blood Donors. Clin. Chem.
47: 1879-1884
[Abstract][Full Text]
Kunicki, T. J., Ruggeri, Z. M.
(2001). Platelet Collagen Receptors and Risk Prediction in Stroke and Coronary Artery Disease. Circulation
104: 1451-1453
[Full Text]
Feng, D., Lindpaintner, K., Larson, M. G., O'Donnell, C. J., Lipinska, I., Sutherland, P. A., Mittleman, M., Muller, J. E., D'Agostino, R. B., Levy, D., Tofler, G. H.
(2001). Platelet Glycoprotein IIIa PlA Polymorphism, Fibrinogen, and Platelet Aggregability: The Framingham Heart Study. Circulation
104: 140-144
[Abstract][Full Text]
Wu, K. K., Willerson, J. T.
(2001). Monitoring Platelet Function in Glycoprotein IIb/IIIa Inhibitor Therapy. Circulation
103: 2528-2530
[Full Text]
Spooner, P. M., Albert, C., Benjamin, E. J., Boineau, R., Elston, R. C., George, A. L. Jr, Jouven, X., Kuller, L. H., MacCluer, J. W., Marban, E., Muller, J. E., Schwartz, P. J., Siscovick, D. S., Tracy, R. P., Zareba, W., Zipes, D. P.
(2001). Sudden Cardiac Death, Genes, and Arrhythmogenesis : Consideration of New Population and Mechanistic Approaches From a National Heart, Lung, and Blood Institute Workshop, Part II. Circulation
103: 2447-2452
[Abstract][Full Text]
Bennett, J. S., Catella-Lawson, F., Rut, A. R., Vilaire, G., Qi, W., Kapoor, S. C., Murphy, S., FitzGerald, G. A.
(2001). Effect of the PlA2 alloantigen on the function of {beta}3-integrins in platelets. Blood
97: 3093-3099
[Abstract][Full Text]
Williams, M. S., Bray, P. F.
(2001). Genetics of Arterial Prothrombotic Risk States. Exp. Biol. Med.
226: 409-419
[Abstract][Full Text]
Boudreaux, M. K., Lipscomb, D. L.
(2001). Clinical, Biochemical, and Molecular Aspects of Glanzmann's Thrombasthenia in Humans and Dogs. Vet Pathol
38: 249-260
[Abstract][Full Text]
Walter, D.H, Schachinger, V, Elsner, M, Mach, S, Dimmeler, S, Auch-Schwelk, W, Zeiher, A.M
(2001). Statin therapy is associated with reduced restenosis rates after coronary stent implantation in carriers of the PlA2allele of the platelet glycoprotein IIIa gene. Eur Heart J
22: 587-595
[Abstract]
Ilveskero, S., Siljander, P., Lassila, R.
(2001). Procoagulant Activity on Platelets Adhered to Collagen or Plasma Clot. Arterioscler. Thromb. Vasc. Bio.
21: 628-635
[Abstract][Full Text]
Mathew, J. P., Rinder, C. S., Howe, J. G., Fontes, M., Crouch, J., Newman, M. F., Phillips-Bute, B., Smith, B. R.
(2001). Platelet PlA2 polymorphism enhances risk of neurocognitive decline after cardiopulmonary bypass. Ann. Thorac. Surg.
71: 663-666
[Abstract][Full Text]
Sykes, T C F, Fegan, C, Mosquera, D
(2000). Thrombophilia, polymorphisms, and vascular disease. Mol. Pathol.
53: 300-306
[Abstract][Full Text]
Aleksic, N., Juneja, H., Folsom, A. R., Ahn, C., Boerwinkle, E., Chambless, L. E., Wu, K. K.
(2000). Platelet PlA2 Allele and Incidence of Coronary Heart Disease : Results From the Atherosclerosis Risk In Communities (ARIC) Study. Circulation
102: 1901-1905
[Abstract][Full Text]
Roest, M., Banga, J. D., Grobbee, D. E., de Groot, P. G., Sixma, J. J., Tempelman, M. J., van der Schouw, Y. T.
(2000). Homozygosity for 807 T Polymorphism in {alpha}2 Subunit of Platelet {alpha}2{beta}1 Is Associated With Increased Risk of Cardiovascular Mortality in High-Risk Women. Circulation
102: 1645-1650
[Abstract][Full Text]
Mikkelsson, J., Perola, M., Laippala, P., Penttila, A., Karhunen, P. J.
(2000). Glycoprotein IIIa PlA1/A2 polymorphism and sudden cardiac death. J Am Coll Cardiol
36: 1317-1323
[Abstract][Full Text]
Hassan, A., Markus, H. S.
(2000). Genetics and ischaemic stroke. Brain
123: 1784-1812
[Abstract][Full Text]
Kastrati, A., Koch, W., Gawaz, M., Mehilli, J., Bottiger, C., Schomig, K., von Beckerath, N., Schomig, A.
(2000). PlA polymorphism of glycoprotein IIIa and risk of adverse events after coronary stent placement. J Am Coll Cardiol
36: 84-89
[Abstract][Full Text]
Goldschmidt-Clermont, P. J., Cooke, G. E., Eaton, G. M., Binkley, P. F.
(2000). PlA2, a variant of GPIIIa implicated in coronary thromboembolic complications. J Am Coll Cardiol
36: 90-93
[Full Text]
Yokota, M., Ichihara, S., Lin, T.-L., Nakashima, N., Yamada, Y.
(2000). Association of a T29->C Polymorphism of the Transforming Growth Factor-{beta}1 Gene With Genetic Susceptibility to Myocardial Infarction in Japanese. Circulation
101: 2783-2787
[Abstract][Full Text]
Wilcox, D. A., Olsen, J. C., Ishizawa, L., Bray, P. F., French, D. L., Steeber, D. A., Bell, W. R., Griffith, M., White, G. C. II
(2000). Megakaryocyte-targeted synthesis of the integrin beta 3-subunit results in the phenotypic correction of Glanzmann thrombasthenia. Blood
95: 3645-3651
[Abstract][Full Text]
Michelson, A. D., Furman, M. I., Goldschmidt-Clermont, P., Mascelli, M. A., Hendrix, C., Coleman, L., Hamlington, J., Barnard, M. R., Kickler, T., Christie, D. J., Kundu, S., Bray, P. F.
(2000). Platelet GP IIIa PlA Polymorphisms Display Different Sensitivities to Agonists. Circulation
101: 1013-1018
[Abstract][Full Text]
Lane, D. A., Grant, P. J.
(2000). Role of hemostatic gene polymorphisms in venous and arterial thrombotic disease. Blood
95: 1517-1532
[Full Text]
Matsubara, Y., Murata, M., Maruyama, T., Handa, M., Yamagata, N., Watanabe, G., Saruta, T., Ikeda, Y.
(2000). Association between diabetic retinopathy and genetic variations in alpha 2beta 1 integrin, a platelet receptor for collagen. Blood
95: 1560-1564
[Abstract][Full Text]
Bussel, J. B., Kunicki, T. J., Michelson, A. D.
(2000). Platelets: New Understanding of Platelet Glycoproteins and Their Role in Disease. ASH Education Book
2000: 222-240
[Abstract][Full Text]
SALIDO, E., MARTÍN, B., BARRIOS, Y., LINARES, J. D., HERNÁNDEZ, D., COBOS, M., CHECA, M. D., HORTAL, L., FERNÁNDEZ, A., GARCÍA, J. J., TORRES, A.
(1999). The PlA2 Polymorphism of the Platelet Glycoprotein IIIA Gene as a Risk Factor for Acute Renal Allograft Rejection. J. Am. Soc. Nephrol.
10: 2599-2605
[Abstract][Full Text]
Batalla, A., Reguero, J. R., Cubero, G. I., Coto, E.
(1999). Prothrombotic Genetic Risk Factors and Myocardial Infarction at Young Age. Blood
94: 3959-3960
[Full Text]
Hooper, W. C., Lally, C., Austin, H., Benson, J., Dilley, A., Wenger, N. K., Whitsett, C., Rawlins, P., Evatt, B. L.
(1999). The Relationship Between Polymorphisms in the Endothelial Cell Nitric Oxide Synthase Gene and the Platelet GPIIIa Gene With Myocardial Infarction and Venous Thromboembolism in African Americans. Chest
116: 880-886
[Abstract][Full Text]
Cheng, S., Grow, M. A., Pallaud, C., Klitz, W., Erlich, H. A., Visvikis, S., Chen, J. J., Pullinger, C. R., Malloy, M. J., Siest, G., Kane, J. P.
(1999). A Multilocus Genotyping Assay for Candidate Markers of Cardiovascular Disease Risk. Genome Res
9: 936-949
[Abstract][Full Text]
Mikkelsson, J., Perola, M., Laippala, P., Savolainen, V., Pajarinen, J., Lalu, K., Penttila, A., Karhunen, P. J.
(1999). Glycoprotein IIIa PlA Polymorphism Associates With Progression of Coronary Artery Disease and With Myocardial Infarction in an Autopsy Series of Middle-Aged Men Who Died Suddenly. Arterioscler. Thromb. Vasc. Bio.
19: 2573-2578
[Abstract][Full Text]
Ardissino, D., Mannucci, P.M., Merlini, P.A., Duca, F., Fetiveau, R., Tagliabue, L., Tubaro, M., Galvani, M., Ottani, F., Ferrario, M., Corral, J., Margaglione, M.
(1999). Prothrombotic Genetic Risk Factors in Young Survivors of Myocardial Infarction. Blood
94: 46-51
[Abstract][Full Text]
Unkelbach, K., Gardemann, A., Kostrzewa, M., Philipp, M., Tillmanns, H., Haberbosch, W.
(1999). A New Promoter Polymorphism in the Gene of Lipopolysaccharide Receptor CD14 Is Associated With Expired Myocardial Infarction in Patients With Low Atherosclerotic Risk Profile. Arterioscler. Thromb. Vasc. Bio.
19: 932-938
[Abstract][Full Text]
Feng, D., Lindpaintner, K., Larson, M. G., Rao, V. S., O'Donnell, C. J., Lipinska, I., Schmitz, C., Sutherland, P. A., Silbershatz, H., D'Agostino, R. B., Muller, J. E., Myers, R. H., Levy, D., Tofler, G. H.
(1999). Increased Platelet Aggregability Associated With Platelet GPIIIa PlA2 Polymorphism : The Framingham Offspring Study. Arterioscler. Thromb. Vasc. Bio.
19: 1142-1147
[Abstract][Full Text]
Kastrati, A., Schomig, A., Seyfarth, M., Koch, W., Elezi, S., Bottiger, C., Mehilli, J., Schomig, K., von Beckerath, N.
(1999). PlA Polymorphism of Platelet Glycoprotein IIIa and Risk of Restenosis After Coronary Stent Placement. Circulation
99: 1005-1010
[Abstract][Full Text]
Anderson, J. L., King, G. J., Bair, T. L., Elmer, S. P., Muhlestein, J. B., Habashi, J., Carlquist, J. F.
(1999). Associations between a polymorphism in the gene encoding glycoprotein IIIa and myocardial infarction or coronary artery disease. J Am Coll Cardiol
33: 727-733
[Abstract][Full Text]
Bihour, C., Durrieu-Jais, C., Macchi, L., Poujol, C., Coste, P., Besse, P., Nurden, P., Nurden, A. T.
(1999). Expression of Markers of Platelet Activation and the Interpatient Variation in Response to Abciximab. Arterioscler. Thromb. Vasc. Bio.
19: 212-219
[Abstract][Full Text]
Gawaz, M., Neumann, F.-J., Schomig, A.
(1999). Evaluation of Platelet Membrane Glycoproteins in Coronary Artery Disease : Consequences for Diagnosis and Therapy. Circulation
99
: e1-e11
[Full Text]
Wang, R., Newman, P. J.
(1998). Adhesive and Signaling Properties of a Naturally Occurring Allele of Glycoprotein IIIa With an Amino Acid Substitution Within the Ligand Binding Domain---The Pena/Penb Platelet Alloantigenic Epitopes. Blood
92: 3260-3267
[Abstract][Full Text]
Gonzalez-Conejero, R., Lozano, M. L., Rivera, J., Corral, J., Iniesta, J. A., Moraleda, J. M., Vicente, V.
(1998). Polymorphisms of Platelet Membrane Glycoprotein Ibalpha Associated With Arterial Thrombotic Disease. Blood
92: 2771-2776
[Abstract][Full Text]
Batalla, A., Cubero, G. I., Reguero, J. R., Coto, E., Carter, A. M., Grant, B. P. J.
(1998). Platelet PlA Polymorphism, Myocardial Infarction, and Extent of Coronary Artery Disease • Response. Circulation
98: 826-827
[Full Text]
Carter, A. M., Catto, A. J., Bamford, J. M., Grant, P. J.
(1998). Platelet GP IIIa PlA and GP Ib Variable Number Tandem Repeat Polymorphisms and Markers of Platelet Activation in Acute Stroke. Arterioscler. Thromb. Vasc. Bio.
18: 1124-1131
[Abstract][Full Text]
Berger, G. M. B., Pegoraro, R. J., Patel, S. B., Naidu, P., Rom, L., Hidaka, H., Marais, A. D., Jadhav, A., Naoumova, R. P., Thompson, G. R.
(1998). HMG-CoA reductase is not the site of the primary defect in phytosterolemia. J. Lipid Res.
39: 1046-1054
[Abstract][Full Text]
Wagner, K. R., Giles, W. H., Johnson, C. J., Ou, C.-Y., Bray, P. F., Goldschmidt-Clermont, P. J., Croft, J. B., Brown, V. K., Stern, B. J., Feeser, B. R., Buchholz, D. W., Earley, C. J., Macko, R. F., McCarter, R. J., Sloan, M. A., Stolley, P. D., Wityk, R. J., Wozniak, M. A., Price, T. R., Kittner, S. J.
(1998). Platelet Glycoprotein Receptor IIIa Polymorphism P1A2 and Ischemic Stroke Risk : The Stroke Prevention in Young Women Study. Stroke
29: 581-585
[Abstract][Full Text]
Simoni, M., Gromoll, J., Nieschlag, E.
(1997). The Follicle-Stimulating Hormone Receptor: Biochemistry, Molecular Biology, Physiology, and Pathophysiology. Endocr. Rev.
18: 739-773
[Abstract][Full Text]
Murata, M., Matsubara, Y., Kawano, K., Zama, T., Aoki, N., Yoshino, H., Watanabe, G., Ishikawa, K., Ikeda, Y.
(1997). Coronary Artery Disease and Polymorphisms in a Receptor Mediating Shear Stress–Dependent Platelet Activation. Circulation
96: 3281-3286
[Abstract][Full Text]
Carter, A. M., Ossei-Gerning, N., Wilson, I. J., Grant, P. J.
(1997). Association of the Platelet PlA Polymorphism of Glycoprotein IIb/IIIa and the Fibrinogen Bß 448 Polymorphism With Myocardial Infarction and Extent of Coronary Artery Disease. Circulation
96: 1424-1431
[Abstract][Full Text]
Carlsson, L. E., Greinacher, A., Spitzer, C., Walther, R., Kessler, C.
(1997). Polymorphisms of the Human Platelet Antigens HPA-1, HPA-2, HPA-3, and HPA-5 on the Platelet Receptors for Fibrinogen (GPIIb/IIIa), von Willebrand Factor (GPIb/IX), and Collagen (GPIa/IIa) Are Not Correlated With an Increased Risk for Stroke. Stroke
28: 1392-1395
[Abstract][Full Text]
Burke, A. P., Farb, A., Malcom, G. T., Liang, Y.-h., Smialek, J., Virmani, R.
(1997). Coronary Risk Factors and Plaque Morphology in Men with Coronary Disease Who Died Suddenly. NEJM
336: 1276-1282
[Abstract][Full Text]
Samani, N. J., Lodwick, D.
(1997). Glycoprotein IIIa polymorphism and risk of myocardial infarction. Cardiovasc Res
33: 693-697
[Abstract]
Ammar, T., Scudder, L. E., Coller, B. S.
(1997). In Vitro Effects of the Platelet Glycoprotein IIb/IIIa Receptor Antagonist c7E3 Fab on the Activated Clotting Time. Circulation
95: 614-617
[Abstract][Full Text]
Previous
X174 DNA cut with HaeIII, which was used as a size marker. Panel C shows the results of reverse dot blot hybridization with the DNA shown in Panel B. Filters are shown with PlA1-allele–specific oligonucleotides at the top and PlA2-allele–specific oligonucleotides at the bottom.