Common melanocortin-3 receptor variants are not associated with obesity, although rs3746619 does influence weight in obe
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ORIGINAL ARTICLE
Common melanocortin-3 receptor variants are not associated with obesity, although rs3746619 does influence weight in obese individuals Doreen Zegers • Sigri Beckers • Ilse L. Mertens Luc F. Van Gaal • Wim Van Hul
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Received: 7 May 2010 / Accepted: 20 August 2010 / Published online: 23 October 2010 Ó Springer Science+Business Media, LLC 2010
Abstract The melanocortin-3 receptor is a vital link in the leptin–melanocortin signaling pathway in the brain and has a role in the regulation of energy homeostasis. It was hypothesized that common polymorphisms in MC3R could increase susceptibility for the development of obesity, but different studies have led to contradictory results. In this study, we investigated the association of SNPs in MC3R with the development of obesity in an extensive Caucasian population. Using the HapMap, we selected two tagSNPs (rs6127698 and rs3746619) that cover all of the common genetic variation in MC3R and genotyped them in 1008 obese cases and 313 normal weight controls. Statistical analysis of the data showed that none of the analyzed SNPs were associated with obesity. However, linear regression analysis did show that SNP rs3746619 has an influence on weight (P = 0.015) in the obese population only. Furthermore, a trend for association with BMI in the obese population was observed for this SNP (P = 0.039). Taken together, these data are consistent with the involvement of rs3746619 in weight regulation among obese individuals. However, further research including replication of our results is necessary to elucidate the role of MC3R in complex obesity. Keywords MC3R Obesity Genetics Association study
D. Zegers S. Beckers W. Van Hul (&) Department of Medical Genetics, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium e-mail: [email protected] I. L. Mertens L. F. Van Gaal Department of Endocrinology, Diabetology and Metabolism, Antwerp University Hospital, Antwerp, Belgium
Introduction The melancortin-3 receptor (MC3R) belongs to the family of seven transmembrane (7TM) G-protein coupled melanocortin receptors (MCRs) [1]. Together with the wellknown melanocortin-4 receptor (MC4R), MC3R is mainly expressed in the brain. The seven transmembrane (7TM) receptor is predominantly expressed in several nuclei of the hypothalamus that are involved in regulating energy metabolism [1–3] and plays an important role in the leptin– melanocortin signaling pathway in the brain that regulates energy metabolism. By studying Mc3r and Mc4r deficient mice, the role of both MC3R and MC4R receptors in energy homeostasis was demonstrated [4, 5]. It was shown that Mc3r-/- mice display an increase in adipose mass of *50–60% and a higher feed efficiency compared to wildtype (WT) littermates, though they are hypophagic and maintain a normal metabolism. It is, therefore, suggested that in the absence of Mc3r, nutrients are preferentially partitioned into fat mass [5, 6]. This indicates that the MC3R receptor is involved in the regulation of energy metabolism by regulating t
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