Background Melanocortin 4 receptor (MC4R) deficiency is thecommonest monogenic form of obesity. However, the clinical spectrumand mode of inheritance have not been defined, pathophysiologicalmechanisms leading to obesity are poorly understood, and thereis little information regarding genotype–phenotype correlations.
Methods We determined the nucleotide sequence of the MC4R genein 500 probands with severe childhood obesity. Family studieswere undertaken to examine cosegregation of identified mutationswith obesity. Subjects with MC4R deficiency underwent metabolicand endocrine evaluation; the results were correlated with thesignaling properties of mutant receptors.
Results Twenty-nine probands (5.8 percent) had mutations inMC4R; 23 were heterozygous, and 6 were homozygous. Mutationcarriers had severe obesity, increased lean mass, increasedlinear growth, hyperphagia, and severe hyperinsulinemia; homozygoteswere more severely affected than heterozygotes. Subjects withmutations retaining residual signaling capacity had a less severephenotype.
Conclusions Mutations in MC4R result in a distinct obesity syndromethat is inherited in a codominant manner. Mutations leadingto complete loss of function are associated with a more severephenotype. The correlation between the signaling propertiesof these mutant receptors and energy intake emphasizes the keyrole of this receptor in the control of eating behavior in humans.
Source Information
From the Genetics of Obesity Collaborative Group (T.C.) and the University Departments of Medicine and Clinical Biochemistry (I.S.F., J.M.K., G.H.S.Y., E.J.L., S.O.'R.), Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge, United Kingdom.
Address reprint requests to Dr. O'Rahilly at the Cambridge Institute for Medical Research, Addenbrooke's Hospital, Cambridge CB2 2QQ, United Kingdom, or at sorahill{at}hgmp.mrc.ac.uk.
Bouchard, C.
(2009). Childhood obesity: are genetic differences involved?. Am. J. Clin. Nutr.
89: 1494S-1501S
[Abstract][Full Text]
Chan, L. F., Webb, T. R., Chung, T.-T., Meimaridou, E., Cooray, S. N., Guasti, L., Chapple, J. P., Egertova, M., Elphick, M. R., Cheetham, M. E., Metherell, L. A., Clark, A. J. L.
(2009). MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proc. Natl. Acad. Sci. USA
106: 6146-6151
[Abstract][Full Text]
Peter, J.-C., Bekel, A., Lecourt, A.-C., Zipfel, G., Eftekhari, P., Nesslinger, M., Breidert, M., Muller, S., Kessler, L., Hofbauer, K. G.
(2009). Anti-Melanocortin-4 Receptor Autoantibodies in Obesity. J. Clin. Endocrinol. Metab.
94: 793-800
[Abstract][Full Text]
Friedman, J. M
(2009). Leptin at 14 y of age: an ongoing story. Am. J. Clin. Nutr.
89: 973S-979S
[Abstract][Full Text]
Haskell-Luevano, C., Schaub, J. W., Andreasen, A., Haskell, K. R., Moore, M. C., Koerper, L. M., Rouzaud, F., Baker, H. V., Millard, W. J., Walter, G., Litherland, S. A., Xiang, Z.
(2009). Voluntary exercise prevents the obese and diabetic metabolic syndrome of the melanocortin-4 receptor knockout mouse. FASEB J.
23: 642-655
[Abstract][Full Text]
Hooper, L. M., Burnham, J. J., Richey, R.
(2009). Select Parent and Family System Correlates of Adolescent Current Weight Status: A Pilot Study. The Family Journal
17: 14-21
[Abstract]
Greenfield, J. R., Miller, J. W., Keogh, J. M., Henning, E., Satterwhite, J. H., Cameron, G. S., Astruc, B., Mayer, J. P., Brage, S., See, T. C., Lomas, D. J., O'Rahilly, S., Farooqi, I. S.
(2009). Modulation of Blood Pressure by Central Melanocortinergic Pathways. NEJM
360: 44-52
[Abstract][Full Text]
Tan, K., Pogozheva, I. D., Yeo, G. S. H., Hadaschik, D., Keogh, J. M., Haskell-Leuvano, C., O'Rahilly, S., Mosberg, H. I., Farooqi, I. S.
(2009). Functional Characterization and Structural Modeling of Obesity Associated Mutations in the Melanocortin 4 Receptor. Endocrinology
150: 114-125
[Abstract][Full Text]
Leibel, R. L.
(2008). Energy In, Energy Out, and the Effects of Obesity-Related Genes. NEJM
359: 2603-2604
[Full Text]
Krakoff, J., Ma, L., Kobes, S., Knowler, W. C., Hanson, R. L., Bogardus, C., Baier, L. J.
(2008). Lower Metabolic Rate in Individuals Heterozygous for Either a Frameshift or a Functional Missense MC4R Variant. Diabetes
57: 3267-3272
[Abstract][Full Text]
O'Rahilly, S., Farooqi, I. S.
(2008). Human Obesity: A Heritable Neurobehavioral Disorder That Is Highly Sensitive to Environmental Conditions. Diabetes
57: 2905-2910
[Full Text]
Blakemore, A. I. F., Froguel, P.
(2008). Is Obesity Our Genetic Legacy?. J. Clin. Endocrinol. Metab.
93: s51-s56
[Abstract][Full Text]
Bougneres, P., Pantalone, L., Linglart, A., Rothenbuhler, A., Le Stunff, C.
(2008). Endocrine Manifestations of the Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neural Tumor Syndrome in Childhood. J. Clin. Endocrinol. Metab.
93: 3971-3980
[Abstract][Full Text]
Stutzmann, F., Tan, K., Vatin, V., Dina, C., Jouret, B., Tichet, J., Balkau, B., Potoczna, N., Horber, F., O'Rahilly, S., Farooqi, I. S., Froguel, P., Meyre, D.
(2008). Prevalence of Melanocortin-4 Receptor Deficiency in Europeans and Their Age-Dependent Penetrance in Multigenerational Pedigrees. Diabetes
57: 2511-2518
[Abstract][Full Text]
Kublaoui, B. M., Gemelli, T., Tolson, K. P., Wang, Y., Zinn, A. R.
(2008). Oxytocin Deficiency Mediates Hyperphagic Obesity of Sim1 Haploinsufficient Mice. Mol. Endocrinol.
22: 1723-1734
[Abstract][Full Text]
Mark, A. L.
(2008). Dietary Therapy for Obesity: An Emperor With No Clothes. Hypertension
51: 1426-1434
[Full Text]
Crowley, V. E F
(2008). Overview of human obesity and central mechanisms regulating energy homeostasis. Ann Clin Biochem
45: 245-255
[Abstract][Full Text]
Bloom, S. R., Kuhajda, F. P., Laher, I., Pi-Sunyer, X., Ronnett, G. V., Tan, T. M.M., Weigle, D. S.
(2008). The Obesity Epidemic: Pharmacological Challenges. Mol. Interv.
8: 82-98
[Abstract][Full Text]
Kapur, A., Samaniego, P., Thakur, G. A., Makriyannis, A., Abood, M. E.
(2008). Mapping the Structural Requirements in the CB1 Cannabinoid Receptor Transmembrane Helix II for Signal Transduction. J. Pharmacol. Exp. Ther.
325: 341-348
[Abstract][Full Text]
Chehab, F. F.
(2008). Minireview: Obesity and LipOdystrophy--Where Do the Circles Intersect?. Endocrinology
149: 925-934
[Abstract][Full Text]
Lam, D. D., Przydzial, M. J., Ridley, S. H., Yeo, G. S. H., Rochford, J. J., O'Rahilly, S., Heisler, L. K.
(2008). Serotonin 5-HT2C Receptor Agonist Promotes Hypophagia via Downstream Activation of Melanocortin 4 Receptors. Endocrinology
149: 1323-1328
[Abstract][Full Text]
Ghoussaini, M., Vatin, V., Lecoeur, C., Abkevich, V., Younus, A., Samson, C., Wachter, C., Heude, B., Tauber, M., Tounian, P., Hercberg, S., Weill, J., Levy-Marchal, C., Le Stunff, C., Bougneres, P., Froguel, P., Meyre, D.
(2007). Genetic Study of the Melanin-Concentrating Hormone Receptor 2 in Childhood and Adulthood Severe Obesity. J. Clin. Endocrinol. Metab.
92: 4403-4409
[Abstract][Full Text]
Sookoian, S., Pirola, C. J.
(2007). Review: Genetics of the cardiometabolic syndrome: new insights and therapeutic implications. Ther Adv Cardiovasc Dis
1: 37-47
[Abstract]
Hainerova, I., Larsen, L. H., Holst, B., Finkova, M., Hainer, V., Lebl, J., Hansen, T., Pedersen, O.
(2007). Melanocortin 4 Receptor Mutations in Obese Czech Children: Studies of Prevalence, Phenotype Development, Weight Reduction Response, and Functional Analysis. J. Clin. Endocrinol. Metab.
92: 3689-3696
[Abstract][Full Text]
Farooqi, I. S., Volders, K., Stanhope, R., Heuschkel, R., White, A., Lank, E., Keogh, J., O'Rahilly, S., Creemers, J. W. M.
(2007). Hyperphagia and Early-Onset Obesity due to a Novel Homozygous Missense Mutation in Prohormone Convertase 1/3. J. Clin. Endocrinol. Metab.
92: 3369-3373
[Abstract][Full Text]
Stutzmann, F., Vatin, V., Cauchi, S., Morandi, A., Jouret, B., Landt, O., Tounian, P., Levy-Marchal, C., Buzzetti, R., Pinelli, L., Balkau, B., Horber, F., Bougneres, P., Froguel, P., Meyre, D.
(2007). Non-synonymous polymorphisms in melanocortin-4 receptor protect against obesity: the two facets of a Janus obesity gene. Hum Mol Genet
16: 1837-1844
[Abstract][Full Text]
Chen, M., Cai, M., Aprahamian, C. J., Georgeson, K. E., Hruby, V., Harmon, C. M., Yang, Y.
(2007). Contribution of the Conserved Amino Acids of the Melanocortin-4 Receptor in D-[Nle4,Phe7]-{alpha}-Melanocyte-stimulating Hormone Binding and Signaling. J. Biol. Chem.
282: 21712-21719
[Abstract][Full Text]
Lee, M., Kim, A., Chua, S. C. Jr., Obici, S., Wardlaw, S. L.
(2007). Transgenic MSH overexpression attenuates the metabolic effects of a high-fat diet. Am. J. Physiol. Endocrinol. Metab.
293: E121-E131
[Abstract][Full Text]
Pereira, R. M. C., Aguiar-Oliveira, M. H., Sagazio, A., Oliveira, C. R. P., Oliveira, F. T., Campos, V. C., Farias, C. T., Vicente, T. A. R., Gois, M. B. Jr, Oliveira, J. L. M., Marques-Santos, C., Rocha, I. E. S., Barreto-Filho, J. A. S., Salvatori, R.
(2007). Heterozygosity for a Mutation in the Growth Hormone-Releasing Hormone Receptor Gene Does Not Influence Adult Stature, But Affects Body Composition. J. Clin. Endocrinol. Metab.
92: 2353-2357
[Abstract][Full Text]
Shimizu, H., Inoue, K., Mori, M.
(2007). The leptin-dependent and -independent melanocortin signaling system: regulation of feeding and energy expenditure. J Endocrinol
193: 1-9
[Abstract][Full Text]
Santoro, N., Perrone, L., Cirillo, G., Raimondo, P., Amato, A., Brienza, C., del Giudice, E. M.
(2007). Effect of the melanocortin-3 receptor C17A and G241A variants on weight loss in childhood obesity. Am. J. Clin. Nutr.
85: 950-953
[Abstract][Full Text]
Mohammad, S., Baldini, G., Granell, S., Narducci, P., Martelli, A. M., Baldini, G.
(2007). Constitutive Traffic of Melanocortin-4 Receptor in Neuro2A Cells and Immortalized Hypothalamic Neurons. J. Biol. Chem.
282: 4963-4974
[Abstract][Full Text]
Rompler, H., Staubert, C., Thor, D., Schulz, A., Hofreiter, M., Schoneberg, T.
(2007). G Protein-Coupled Time Travel: Evolutionary Aspects of GPCR Research. Mol. Interv.
7: 17-25
[Abstract][Full Text]
Farooqi, I. S., Wangensteen, T., Collins, S., Kimber, W., Matarese, G., Keogh, J. M., Lank, E., Bottomley, B., Lopez-Fernandez, J., Ferraz-Amaro, I., Dattani, M. T., Ercan, O., Myhre, A. G., Retterstol, L., Stanhope, R., Edge, J. A., McKenzie, S., Lessan, N., Ghodsi, M., De Rosa, V., Perna, F., Fontana, S., Barroso, I., Undlien, D. E., O'Rahilly, S.
(2007). Clinical and Molecular Genetic Spectrum of Congenital Deficiency of the Leptin Receptor. NEJM
356: 237-247
[Abstract][Full Text]
Farooqi, I. S., O'Rahilly, S.
(2006). Genetics of Obesity in Humans. Endocr. Rev.
27: 710-718
[Abstract][Full Text]
Foster-Schubert, K. E., Cummings, D. E.
(2006). Emerging Therapeutic Strategies for Obesity. Endocr. Rev.
27: 779-793
[Abstract][Full Text]
Tung, Y. C. L., Piper, S. J., Yeung, D., O'Rahilly, S., Coll, A. P.
(2006). A Comparative Study of the Central Effects of Specific Proopiomelancortin (POMC)-Derived Melanocortin Peptides on Food Intake and Body Weight in Pomc Null Mice. Endocrinology
147: 5940-5947
[Abstract][Full Text]
Sebag, J. A., Hinkle, P. M.
(2006). Regulation of Endogenous Melanocortin-4 Receptor Expression and Signaling by Glucocorticoids. Endocrinology
147: 5948-5955
[Abstract][Full Text]
Grosse, J., Tarnow, P., Rompler, H., Schneider, B., Sedlmeier, R., Huffstadt, U., Korthaus, D., Nehls, M., Wattler, S., Schoneberg, T., Biebermann, H., Augustin, M.
(2006). N-ethyl-N-nitrosourea-based generation of mouse models for mutant G protein-coupled receptors. Physiol. Genomics
26: 209-217
[Abstract][Full Text]
O'Rahilly, S., Farooqi, I.S.
(2006). Genetics of obesity. Phil Trans R Soc B
361: 1095-1105
[Abstract][Full Text]
Kublaoui, B. M., Zinn, A. R.
(2006). MC4R Mutations--Weight before Screening!. J. Clin. Endocrinol. Metab.
91: 1671-1672
[Full Text]
Nicholson, J. R., Kohler, G., Schaerer, F., Senn, C., Weyermann, P., Hofbauer, K. G.
(2006). Peripheral Administration of a Melanocortin 4-Receptor Inverse Agonist Prevents Loss of Lean Body Mass in Tumor-Bearing Mice. J. Pharmacol. Exp. Ther.
317: 771-777
[Abstract][Full Text]
Hinney, A., Bettecken, T., Tarnow, P., Brumm, H., Reichwald, K., Lichtner, P., Scherag, A., Nguyen, T. T., Schlumberger, P., Rief, W., Vollmert, C., Illig, T., Wichmann, H-E., Schafer, H., Platzer, M., Biebermann, H., Meitinger, T., Hebebrand, J.
(2006). Prevalence, Spectrum, and Functional Characterization of Melanocortin-4 Receptor Gene Mutations in a Representative Population-Based Sample and Obese Adults from Germany. J. Clin. Endocrinol. Metab.
91: 1761-1769
[Abstract][Full Text]
Lubrano-Berthelier, C., Dubern, B., Lacorte, J.-M., Picard, F., Shapiro, A., Zhang, S., Bertrais, S., Hercberg, S., Basdevant, A., Clement, K., Vaisse, C.
(2006). Melanocortin 4 Receptor Mutations in a Large Cohort of Severely Obese Adults: Prevalence, Functional Classification, Genotype-Phenotype Relationship, and Lack of Association with Binge Eating. J. Clin. Endocrinol. Metab.
91: 1811-1818
[Abstract][Full Text]
Garcia, M. C., Wernstedt, I., Berndtsson, A., Enge, M., Bell, M., Hultgren, O., Horn, M., Ahren, B., Enerback, S., Ohlsson, C., Wallenius, V., Jansson, J.-O.
(2006). Mature-onset obesity in interleukin-1 receptor I knockout mice.. Diabetes
55: 1205-1213
[Abstract][Full Text]
Hudson, J. I., Lalonde, J. K., Berry, J. M., Pindyck, L. J., Bulik, C. M., Crow, S. J., McElroy, S. L., Laird, N. M., Tsuang, M. T., Walsh, B. T., Rosenthal, N. R., Pope, H. G. Jr
(2006). Binge-eating disorder as a distinct familial phenotype in obese individuals.. Arch Gen Psychiatry
63: 313-319
[Abstract][Full Text]
Ong, K. K., Emmett, P. M., Noble, S., Ness, A., Dunger, D. B., and the ALSPAC Study Team,
(2006). Dietary Energy Intake at the Age of 4 Months Predicts Postnatal Weight Gain and Childhood Body Mass Index. Pediatrics
117: e503-e508
[Abstract][Full Text]
Bronner, G., Sattler, A. M., Hinney, A., Soufi, M., Geller, F., Schafer, H., Maisch, B., Hebebrand, J., Schaefer, J. R.
(2006). The 103I Variant of the Melanocortin 4 Receptor Is Associated with Low Serum Triglyceride Levels. J. Clin. Endocrinol. Metab.
91: 535-538
[Abstract][Full Text]
Hallschmid, M., Smolnik, R., McGregor, G., Born, J., Fehm, H. L.
(2006). Overweight Humans Are Resistant to the Weight-Reducing Effects of Melanocortin4-10. J. Clin. Endocrinol. Metab.
91: 522-525
[Abstract][Full Text]
Druce, M, Bloom, S R
(2006). The regulation of appetite. Arch. Dis. Child.
91: 183-187
[Abstract][Full Text]
Tao, Y.-X., Segaloff, D. L.
(2005). Functional Analyses of Melanocortin-4 Receptor Mutations Identified from Patients with Binge Eating Disorder and Nonobese or Obese Subjects. J. Clin. Endocrinol. Metab.
90: 5632-5638
[Abstract][Full Text]
Feng, N., Young, S. F., Aguilera, G., Puricelli, E., Adler-Wailes, D. C., Sebring, N. G., Yanovski, J. A.
(2005). Co-occurrence of Two Partially Inactivating Polymorphisms of MC3R Is Associated With Pediatric-Onset Obesity. Diabetes
54: 2663-2667
[Abstract][Full Text]
Trevaskis, J., Walder, K., Foletta, V., Kerr-Bayles, L., McMillan, J., Cooper, A., Lee, S., Bolton, K., Prior, M., Fahey, R., Whitecross, K., Morton, G. J., Schwartz, M. W., Collier, G. R.
(2005). Src Homology 3-Domain Growth Factor Receptor-Bound 2-Like (Endophilin) Interacting Protein 1, a Novel Neuronal Protein that Regulates Energy Balance. Endocrinology
146: 3757-3764
[Abstract][Full Text]
Herbeth, B., Aubry, E., Fumeron, F., Aubert, R., Cailotto, F., Siest, G., Visvikis-Siest, S.
(2005). Polymorphism of the 5-HT2A receptor gene and food intakes in children and adolescents: the Stanislas Family Study. Am. J. Clin. Nutr.
82: 467-470
[Abstract][Full Text]
Coll, A. P., Challis, B. G., Lopez, M., Piper, S., Yeo, G. S.H., O'Rahilly, S.
(2005). Proopiomelanocortin-Deficient Mice Are Hypersensitive to the Adverse Metabolic Effects of Glucocorticoids. Diabetes
54: 2269-2276
[Abstract][Full Text]
Buono, P., Pasanisi, F., Nardelli, C., Ieno, L., Capone, S., Liguori, R., Finelli, C., Oriani, G., Contaldo, F., Sacchetti, L.
(2005). Six Novel Mutations in the Proopiomelanocortin and Melanocortin Receptor 4 Genes in Severely Obese Adults Living in Southern Italy. Clin. Chem.
51: 1358-1364
[Abstract][Full Text]
Goldstone, A. P., Patterson, M., Kalingag, N., Ghatei, M. A., Brynes, A. E., Bloom, S. R., Grossman, A. B., Korbonits, M.
(2005). Fasting and Postprandial Hyperghrelinemia in Prader-Willi Syndrome Is Partially Explained by Hypoinsulinemia, and Is Not Due to Peptide YY3-36 Deficiency or Seen in Hypothalamic Obesity Due to Craniopharyngioma. J. Clin. Endocrinol. Metab.
90: 2681-2690
[Abstract][Full Text]
Heid, I M, Vollmert, C, Hinney, A, Doring, A, Geller, F, Lowel, H, Wichmann, H-E, Illig, T, Hebebrand, J, Kronenberg, F, the KORA Group,
(2005). Association of the 103I MC4R allele with decreased body mass in 7937 participants of two population based surveys. J. Med. Genet.
42: e21-e21
[Abstract][Full Text]
Viner, R, Nicholls, D
(2005). Managing obesity in secondary care: a personal practice. Arch. Dis. Child.
90: 385-390
[Abstract][Full Text]
Larsen, L. H., Echwald, S. M., Sorensen, T. I. A., Andersen, T., Wulff, B. S., Pedersen, O.
(2005). Prevalence of Mutations and Functional Analyses of Melanocortin 4 Receptor Variants Identified among 750 Men with Juvenile-Onset Obesity. J. Clin. Endocrinol. Metab.
90: 219-224
[Abstract][Full Text]
Santoro, N., del Giudice, E. M., Cirillo, G., Raimondo, P., Corsi, I., Amato, A., Grandone, A., Perrone, L.
(2004). An Insertional Polymorphism of the Proopiomelanocortin Gene Is Associated with Fasting Insulin Levels in Childhood Obesity. J. Clin. Endocrinol. Metab.
89: 4846-4849
[Abstract][Full Text]
Ma, L., Tataranni, P. A., Bogardus, C., Baier, L. J.
(2004). Melanocortin 4 Receptor Gene Variation Is Associated With Severe Obesity in Pima Indians. Diabetes
53: 2696-2699
[Abstract][Full Text]
Dempfle, A, Hinney, A, Heinzel-Gutenbrunner, M, Raab, M, Geller, F, Gudermann, T, Schafer, H, Hebebrand, J
(2004). Large quantitative effect of melanocortin-4 receptor gene mutations on body mass index. J. Med. Genet.
41: 795-800
[Full Text]
Miller, J., Rosenbloom, A., Silverstein, J.
(2004). Childhood Obesity. J. Clin. Endocrinol. Metab.
89: 4211-4218
[Full Text]
Savontaus, E., Breen, T. L., Kim, A., Yang, L. M., Chua, S. C. Jr., Wardlaw, S. L.
(2004). Metabolic Effects of Transgenic Melanocyte-Stimulating Hormone Overexpression in Lean and Obese Mice. Endocrinology
145: 3881-3891
[Abstract][Full Text]
Speakman, J. R.
(2004). Obesity: The Integrated Roles of Environment and Genetics. J. Nutr.
134: 2090S-2105S
[Abstract][Full Text]
Ten, S., Maclaren, N.
(2004). Insulin Resistance Syndrome in Children. J. Clin. Endocrinol. Metab.
89: 2526-2539
[Abstract][Full Text]
Coll, A. P., Farooqi, I. S., Challis, B. G., Yeo, G. S. H., O'Rahilly, S.
(2004). Proopiomelanocortin and Energy Balance: Insights from Human and Murine Genetics. J. Clin. Endocrinol. Metab.
89: 2557-2562
[Abstract][Full Text]
Archer, Z. A., Rayner, D. V., Mercer, J. G.
(2004). Hypothalamic Gene Expression Is Altered in Underweight but Obese Juvenile Male Sprague-Dawley Rats Fed a High-Energy Diet. J. Nutr.
134: 1369-1374
[Abstract][Full Text]
Lubrano-Berthelier, C., Le Stunff, C., Bougneres, P., Vaisse, C.
(2004). A Homozygous Null Mutation Delineates the Role of the Melanocortin-4 Receptor in Humans. J. Clin. Endocrinol. Metab.
89: 2028-2032
[Abstract][Full Text]
Guo, F., Bakal, K., Minokoshi, Y., Hollenberg, A. N.
(2004). Leptin Signaling Targets the Thyrotropin-Releasing Hormone Gene Promoter in Vivo. Endocrinology
145: 2221-2227
[Abstract][Full Text]
North, K. E., Rose, K. M., Borecki, I. B., Oberman, A., Hunt, S. C., Miller, M. B., Blangero, J., Almasy, L., Pankow, J. S.
(2004). Evidence for a Gene on Chromosome 13 Influencing Postural Systolic Blood Pressure Change and Body Mass Index. Hypertension
43: 780-784
[Abstract][Full Text]
Polotsky, V. Y., Smaldone, M. C., Scharf, M. T., Li, J., Tankersley, C. G., Smith, P. L., Schwartz, A. R., O'Donnell, C. P.
(2004). Impact of interrupted leptin pathways on ventilatory control. J. Appl. Physiol.
96: 991-998
[Abstract][Full Text]
Hansen, J. L., Haunso, S., Brann, M. R., Sheikh, S. P., Weiner, D. M.
(2004). Loss-of-Function Polymorphic Variants of the Human Angiotensin II Type 1 Receptor. Mol. Pharmacol.
65: 770-777
[Abstract][Full Text]
Humphreys, M. H.
(2004). {gamma}-MSH, sodium metabolism, and salt-sensitive hypertension. Am. J. Physiol. Regul. Integr. Comp. Physiol.
286: R417-R430
[Abstract][Full Text]
Santini, F., Maffei, M., Ceccarini, G., Pelosini, C., Scartabelli, G., Rosellini, V., Chiellini, C., Marsili, A., Lisi, S., Tonacchera, M., Agretti, P., Chiovato, L., Mammoli, C., Vitti, P., Pinchera, A.
(2004). Genetic Screening for Melanocortin-4 Receptor Mutations in a Cohort of Italian Obese Patients: Description and Functional Characterization of a Novel Mutation. J. Clin. Endocrinol. Metab.
89: 904-908
[Abstract][Full Text]
Valli-Jaakola, K., Lipsanen-Nyman, M., Oksanen, L., Hollenberg, A. N., Kontula, K., Bjorbaek, C., Schalin-Jantti, C.
(2004). Identification and Characterization of Melanocortin-4 Receptor Gene Mutations in Morbidly Obese Finnish Children and Adults. J. Clin. Endocrinol. Metab.
89: 940-945
[Abstract][Full Text]
Ellacott, K. L.J., Cone, R. D.
(2004). The Central Melanocortin System and the Integration of Short- and Long-term Regulators of Energy Homeostasis. Recent Prog Horm Res
59: 395-408
[Abstract][Full Text]
Farooqi, I.S., O'Rahilly, S.
(2004). Monogenic Human Obesity Syndromes. Recent Prog Horm Res
59: 409-424
[Abstract][Full Text]
Albarado, D. C., McClaine, J., Stephens, J. M., Mynatt, R. L., Ye, J., Bannon, A. W., Richards, W. G., Butler, A. A.
(2004). Impaired Coordination of Nutrient Intake and Substrate Oxidation in Melanocortin-4 Receptor Knockout Mice. Endocrinology
145: 243-252
[Abstract][Full Text]
Pomp, D., Allan, M. F., Wesolowski, S. R.
(2004). Quantitative genomics: Exploring the genetic architecture of complex trait predisposition. J ANIM SCI
82: E300-312
[Abstract][Full Text]
Tarnow, P., Schoneberg, T., Krude, H., Gruters, A., Biebermann, H.
(2003). Mutationally Induced Disulfide Bond Formation within the Third Extracellular Loop Causes Melanocortin 4 Receptor Inactivation in Patients with Obesity. J. Biol. Chem.
278: 48666-48673
[Abstract][Full Text]
Donohoue, P. A., Tao, Y.-X., Collins, M., Yeo, G. S. H., O'Rahilly, S., Segaloff, D. L.
(2003). Deletion of Codons 88-92 of the Melanocortin-4 Receptor Gene: A Novel Deleterious Mutation in an Obese Female. J. Clin. Endocrinol. Metab.
88: 5841-5845
[Abstract][Full Text]
Lubrano-Berthelier, C., Cavazos, M., Le Stunff, C., Haas, K., Shapiro, A., Zhang, S., Bougneres, P., Vaisse, C.
(2003). The Human MC4R Promoter: Characterization and Role in Obesity. Diabetes
52: 2996-3000
[Abstract][Full Text]
Tao, Y.-X., Segaloff, D. L.
(2003). Functional Characterization of Melanocortin-4 Receptor Mutations Associated with Childhood Obesity. Endocrinology
144: 4544-4551
[Abstract][Full Text]
Guttmacher, A. E., Collins, F. S.
(2003). Welcome to the Genomic Era. NEJM
349: 996-998
[Full Text]
O'Rahilly, S., Farooqi, I. S., Yeo, G. S. H., Challis, B. G.
(2003). Minireview: Human Obesity--Lessons from Monogenic Disorders. Endocrinology
144: 3757-3764
[Abstract][Full Text]
Gotoda, T., Herpertz, S., Siffert, W., Hebebrand, J., Farooqi, I. S., Yeo, G. S., O'Rahilly, S., Kral, J. G., Lentes, K.-U., Horber, F.
(2003). Binge Eating as a Phenotype of Melanocortin 4 Receptor Gene Mutations. NEJM
349: 606-609
[Full Text]
Previous
