Ghoussaini Maya, Vatin Vincent, Lecoeur Cécile, Abkevich Victor, Younus Adib, Samson Chantal, Wachter Christophe, Heude Barbara, Tauber Maïté, Tounian Patrick, Hercberg Serge, Weill Jacques, Levy-Marchal Claire, Le Stunff Catherine, Bougnères Pierre, Froguel Philippe, Meyre David
Centre National de la Recherche Scientifique Unité Mixte de Recherche 8090-Institute of Biology, Pasteur Institute, 59000 Lille, France.
J Clin Endocrinol Metab. 2007 Nov;92(11):4403-9. doi: 10.1210/jc.2006-2316. Epub 2007 Aug 14.
The melanin-concentrating hormone receptor 2 (MCHR2) is a G protein-coupled receptor for melanin-concentrating hormone, a neuropeptide that plays an important role in feeding behaviors. MCHR2 maps on chromosome 6q16.3, in a susceptibility locus for childhood obesity.
The aim of this study was to investigate the association between MCHR2 variation and human obesity.
Case control and family-based studies were performed.
A total of 141 obese children and 24 nonobese adult subjects was sequenced, and case-control analyses were conducted using 628 severely obese children and 1,401 controls.
There were 11 single nucleotide polymorphisms (SNPs) identified. We showed nominal association among -38,245 ATG A/G SNP (P = 0.03; 95% confidence interval 1.02-1.34; odds ratio 1.17), A76A T/C SNP (P = 0.03; 95% confidence interval 0.58-0.97; odds ratio 0.75), and childhood obesity. Analysis of 645 trios with childhood obesity supported further the A76A T/C association, showing an overtransmission to obese children of the at risk T allele (59.0%; P = 0.01), especially in children with most severe forms of obesity (Z score of body mass index > 4) (67.0%; P = 0.003). The A76A at risk T allele was also associated with overeating during meals (P = 0.02) in an additional group of 102 nonobese children. None of the MCHR2 variants, including the A76A SNP, showed association with adult severe obesity, although a trend for association of the T allele of this variant with food disinhibition (P = 0.06) and higher hunger (P = 0.09) was found. This variant was not associated with childhood obesity in an independent case-control study, including 1,573 subjects (P = 0.98). Moreover, the A76A SNP did not explain the linkage on the 6q locus.
Our results altogether suggest that MCHR2 is not a major contributor to polygenic obesity and support a modest effect of the A76A SNP on food intake abnormalities in childhood.
黑色素聚集激素受体2（MCHR2）是一种与黑色素聚集激素结合的G蛋白偶联受体，黑色素聚集激素是一种在进食行为中起重要作用的神经肽。MCHR2定位于6号染色体q16.3，该区域是儿童肥胖的一个易感位点。
本研究旨在探讨MCHR2变异与人类肥胖之间的关联。
进行了病例对照研究和基于家系的研究。
对141名肥胖儿童和24名非肥胖成人进行了测序，并使用628名重度肥胖儿童和1401名对照进行病例对照分析。
共鉴定出11个单核苷酸多态性（SNP）。我们发现-38,245 ATG A/G SNP（P = 0.03；95%置信区间1.02 - 1.34；优势比1.17）、A76A T/C SNP（P = 0.03；95%置信区间0.58 - 0.97；优势比0.75）与儿童肥胖之间存在名义上的关联。对645个患有儿童肥胖的三联体进行分析进一步支持了A76A T/C的关联，显示风险T等位基因向肥胖儿童的过度传递（59.0%；P = 0.01），尤其是在最严重肥胖形式的儿童中（体重指数Z评分>4）（67.0%；P = 0.003）。在另外一组102名非肥胖儿童中，A76A风险T等位基因也与进餐时暴饮暴食有关（P = 0.02）。尽管发现该变异的T等位基因与食物抑制（P = 0.06）和更高的饥饿感（P = 0.09）存在关联趋势，但包括A76A SNP在内的所有MCHR2变异均未显示与成人重度肥胖有关。在一项包括1573名受试者的独立病例对照研究中，该变异与儿童肥胖无关（P = 0.98）。此外，A76A SNP无法解释6号染色体q位点的连锁关系。
我们的研究结果总体表明，MCHR2不是多基因肥胖的主要因素，并支持A76A SNP对儿童食物摄入异常有适度影响。
