Background Previous studies have suggested that the variantapolipoprotein (apo) allele apo A-IV-2 may influence the responseof the plasma cholesterol concentration to dietary cholesterol.
Methods We measured plasma lipids and lipoproteins in 11 subjectswho were heterozygous for the apo A-IV-2 allele (apo A-IV-1/2heterozygotes) and a control group of 12 subjects who were homozygousfor the common apo A-IV allele (apo A-IV-1/1 homozygotes) inan outpatient dietary-modification study. (Approximately onein seven persons in the United States is a heterozygote.) Thesubjects consumed a low-cholesterol diet (about 200 mg [0.5mmol] of cholesterol per day) during a two-week run-in period;daily cholesterol intake was then increased to approximately1100 mg (2.8 mmol) by the addition of four egg yolks per day.
Results The fat intake and the ratio of polyunsaturated to saturatedfat were similar in the two groups throughout the study. Afterthree weeks of egg intake, the mean plasma total cholesterolincreased by 22 mg per deciliter (0.57 mmol per liter) in theapo A-IV-1/1 group, but by only 6 mg per deciliter (0.15 mmolper liter) in the apo A-IV-1/2 group (P = 0.05). The mean plasmalow-density lipoprotein cholesterol increased by 19 mg per deciliter(0.49 mmol per liter) in the apo A-IV-1/1 group, but by only1 mg per deciliter (0.03 mmol per liter) in the apo A-IV-1/2group (P = 0.03). There were no changes in the plasma triglycerideor high-density lipoprotein cholesterol concentrations in eithergroup.
Conclusions The apo A-IV-2 allele attenuates the hypercholesterolemicresponse to the short-term ingestion of a very-high-cholesteroldiet and may partially account for the heterogeneous responseto dietary cholesterol. However, cholesterol intake in thisstudy was more than twice that of the general population; whetherthe apo A-IV-2 allele alters responsiveness at lower levelsof cholesterol intake remains to be determined.
Source Information
From the Department of Internal Medicine, Section of Gastroenterology, Bowman Gray School of Medicine, Winston-Salem, N.C.
Address reprint requests to Dr. Weinberg at the Bowman Gray School of Medicine, Medical Center Blvd., Winston-Salem, NC 27257.
Masson, L. F, McNeill, G., Avenell, A.
(2003). Genetic variation and the lipid response to dietary intervention: a systematic review. Am. J. Clin. Nutr.
77: 1098-1111
[Abstract][Full Text]
Woollett, L. A., Buckley, D. D., Yao, L., Jones, P. J. H., Granholm, N. A., Tolley, E. A., Heubi, J. E.
(2003). Effect of ursodeoxycholic acid on cholesterol absorption and metabolism in humans. J. Lipid Res.
44: 935-942
[Abstract][Full Text]
Yao, L., Heubi, J. E., Buckley, D. D., Fierra, H., Setchell, K. D. R., Granholm, N. A., Tso, P., Hui, D. Y., Woollett, L. A.
(2002). Separation of micelles and vesicles within lumenal aspirates from healthy humans: solubilization of cholesterol after a meal. J. Lipid Res.
43: 654-660
[Abstract][Full Text]
Verges, B., Guerci, B., Durlach, V., Galland-Jos, C., Paul, J. L., Lagrost, L., Gambert, P.
(2001). Increased plasma apoA-IV level is a marker of abnormal postprandial lipemia: a study in normoponderal and obese subjects. J. Lipid Res.
42: 2021-2029
[Abstract][Full Text]
Kushner, R. F.
(2001). A New Century: A New Beginning. JPEN J Parenter Enteral Nutr
25: 169-173
Hockey, K. J., Anderson, R. A., Cook, V. R., Hantgan, R. R., Weinberg, R. B.
(2001). Effect of the apolipoprotein A-IV Q360H polymorphism on postprandial plasma triglyceride clearance. J. Lipid Res.
42: 211-217
[Abstract][Full Text]
Denke, M. A., Adams-Huet, B., Nguyen, A. T.
(2000). Individual Cholesterol Variation in Response to a Margarine- or Butter-Based Diet: A Study in Families. JAMA
284: 2740-2747
[Abstract][Full Text]
Weinberg, R. B., Geissinger, B. W., Kasala, K., Hockey, K. J., Terry, J. G., Easter, L., Crouse, J. R.
(2000). Effect of apolipoprotein A-IV genotype and dietary fat on cholesterol absorption in humans. J. Lipid Res.
41: 2035-2041
[Abstract][Full Text]
Ye, S. Q., Kwiterovich, P. O Jr
(2000). Influence of genetic polymorphisms on responsiveness to dietary fat and cholesterol. Am. J. Clin. Nutr.
72
: 1275S-1284S
[Abstract][Full Text]
Weggemans, R. M., Zock, P. L., Meyboom, S., Funke, H., Katan, M. B.
(2000). Apolipoprotein A4-1/2 polymorphism and response of serum lipids to dietary cholesterol in humans. J. Lipid Res.
41: 1623-1628
[Abstract][Full Text]
McNamara, D. J.
(2000). The Impact of Egg Limitations on Coronary Heart Disease Risk: Do the Numbers Add Up?. J. Am. Coll. Nutr.
19: 540S-548
[Abstract][Full Text]
Weinberg, R. B., Anderson, R. A., Cook, V. R., Emmanuel, F., Denefle, P., Hermann, M., Steinmetz, A.
(2000). Structure and interfacial properties of chicken apolipoprotein A-IV. J. Lipid Res.
41: 1410-1418
[Abstract][Full Text]
Marian, A. J., Safavi, F., Ferlic, L., Dunn, J. K., Gotto, A. M., Ballantyne, C. M.
(2000). Interactions between angiotensin-I converting enzyme insertion/deletion polymorphism and response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin: The lipoprotein and coronary atherosclerosis study. J Am Coll Cardiol
35: 89-95
[Abstract][Full Text]
Milner, J. A., Allison, R. G.
(1999). The Role of Dietary Fat in Child Nutrition and Development: Summary of an ASNS Workshop. J. Nutr.
129: 2094-2105
[Full Text]
Clifton, P. M., Noakes, M., Nestel, P. J.
(1998). LDL particle size and LDL and HDL cholesterol changes with dietary fat and cholesterol in healthy subjects. J. Lipid Res.
39: 1799-1804
[Abstract][Full Text]
Carmena-Ramon, R., Ascaso, J. F., Real, J. T., Ordovas, J. M., Carmena, R.
(1998). Genetic Variation at the ApoA-IV Gene Locus and Response to Diet in Familial Hypercholesterolemia. Arterioscler. Thromb. Vasc. Bio.
18: 1266-1274
[Abstract][Full Text]
Tall, A., Welch, C., Applebaum-Bowden, D., Wassef, M.
(1997). Interaction of Diet and Genes in Atherogenesis Report of an NHLBI Working Group. Arterioscler. Thromb. Vasc. Bio.
17: 3326-3331
[Abstract][Full Text]
Jansen, S., Lopez-Miranda, J., Salas, J., Ordovas, J. M., Castro, P., Marin, C., Ostos, M. A., Lopez-Segura, F., Jimenez-Pereperez, J. A., Blanco, A., Perez-Jimenez, F.
(1997). Effect of 347-Serine Mutation in Apoprotein A-IV on Plasma LDL Cholesterol Response to Dietary Fat. Arterioscler. Thromb. Vasc. Bio.
17: 1532-1538
[Abstract][Full Text]
Campos, H., Lopez-Miranda, J., Rodriguez, C., Albajar, M., Schaefer, E. J., Ordovas, J. M.
(1997). Urbanization Elicits a More Atherogenic Lipoprotein Profile in Carriers of the Apolipoprotein A-IV-2 Allele Than in A-IV-1 Homozygotes. Arterioscler. Thromb. Vasc. Bio.
17: 1074-1081
[Abstract][Full Text]
Gylling, H., Kontula, K., Koivisto, U.-M., Miettinen, H. E., Miettinen, T. A.
(1997). Polymorphisms of the Genes Encoding Apoproteins A-I, B, C-III, and E and LDL Receptor, and Cholesterol and LDL Metabolism During Increased Cholesterol Intake: Common Alleles of the Apoprotein E Gene Show the Greatest Regulatory Impact. Arterioscler. Thromb. Vasc. Bio.
17: 38-44
[Abstract][Full Text]
Sehayek, E., Shefer, S., Nguyen, L. B., Ono, J. G., Merkel, M., Breslow, J. L.
(2000). Apolipoprotein E regulates dietary cholesterol absorption and biliary cholesterol excretion: Studies in C57BL/6 apolipoprotein E knockout mice. Proc. Natl. Acad. Sci. USA
97: 3433-3437
[Abstract][Full Text]
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