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The 103I Variant of the Melanocortin 4 Receptor Is Associated with Low Serum Triglyceride Levels

Department of Child and Adolescent Psychiatry and Psychotherapy (G.B., A.H., J.H.), University of Duisburg-Essen, 45147 Essen, Germany; Department of Internal Medicine and Cardiology (A.M.S., M.S., B.M., J.R.S.) and Institute of Medical Biometry and Epidemiology (F.G., H.S.), Philipps University, 35037 Marburg, Germany; and deCODE Genetics (F.G.), 101 Reykjavik, Iceland

Address all correspondence and requests for reprints to: Dr. Günter Brönner, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Duisburg-Essen, Virchowstrasse 174, 45147 Essen, Germany. E-mail: guenter.broenner{at}uni-duisburg-essen.de.

Abstract

Context: The melanocortin 4 receptor (MC4R) is an essential regulator of energy intake and body weight. Recently, the V103I polymorphism of MC4R has been shown to be negatively associated with body mass index. This suggests that serum lipids and blood pressure in individuals carrying the 103I allele might be influenced as well.

Objective: The objective of this study was to determine whether the most common polymorphism of the MC4R, V103I, affects serum lipid levels and/or blood pressure.

Design, Setting, and Participants: The study participants were 1173 consecutive patients undergoing cardiac catheterization; they were genotyped for the rs2229616 GA substitution at codon 103 (V103I polymorphism) of the MC4R gene. Patients had strictly fasted for at least 12 h before blood samples were drawn. The average age of the patients was 60.9 yr; 72% were males.

Main Outcome Measures: The main outcome measures were body mass index, serum lipids, aortic and systolic blood pressure, and MC4R polymorphism V103I.

Results: Heterozygous carriers of the 103I allele had significantly lower triglyceride levels than individuals homozygous for the wild-type allele (127 vs. 168 mg/dl mean total triglyceride; P = 0.001 or 0.009 after Bonferroni adjustment for seven tests). No homozygous carriers of the 103I allele were present in the study population.

Conclusions: Our study suggests an influence of MC4R activity on triglyceride levels in cardiovascular patients.

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