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This version published online on November 8, 2005
Journal of Clinical Endocrinology & Metabolism, doi:10.1210/jc.2005-0919
A more recent version of this article appeared on February 1, 2006
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Submitted on April 27, 2005
Accepted on November 2, 2005

The 103I variant of the melanocortin 4 receptor (MC4R) is associated with low serum triglyceride levels

GÜNTER BRÖNNER*, ALEXANDER M. SATTLER, ANKE HINNEY, MUHIDIEN SOUFI, FRANK GELLER, HELMUT SCHÄFER, BERNHARD MAISCH, JOHANNES HEBEBRAND, and JUERGEN R. SCHAEFER

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

* To whom correspondence should be addressed. E-mail: guenter.broenner{at}uni-duisburg-essen.de.

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 (BMI). This suggests that serum lipids and blood pressure in individuals carrying the 103I allele might be influenced as well.

Objective: To determine whether the most common polymorphism of the MC4R, V103I, affects serum lipid levels and/or blood pressure.

Design, Setting, and Participants: 1173 consecutive patients undergoing cardiac catheterization were genotyped for the rs2229616 G>A substitution at codon 103 (V103I polymorphism) of the melanocortin 4 receptor (MC4R) gene. Patients had strictly fasted for at least 12 h before blood samples were drawn. Average age of the patients was 60.9 yr; 72% were males.

Main Outcome Measures: Body mass index (BMI), 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 7 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.
Key words: genetics • MC4R • lipids • obesity




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