Young E H, Wareham N J, Farooqi S, Hinney A, Hebebrand J, Scherag A, O'rahilly S, Barroso I, Sandhu M S
MRC Epidemiology Unit, Strangeways Research Laboratory, Cambridge, UK.
Int J Obes (Lond). 2007 Sep;31(9):1437-41. doi: 10.1038/sj.ijo.0803609. Epub 2007 Mar 13.
Previous studies have suggested that a variant in the melanocortin-4 receptor (MC4R) gene is important in protecting against common obesity. Larger studies are needed, however, to confirm this relation.
We assessed the association between the V103I polymorphism in the MC4R gene and obesity in three UK population based cohort studies, totalling 8304 individuals. We also did a meta-analysis of relevant studies, involving 10 975 cases and 18 588 controls, to place our findings in context.
In an analysis of all studies, individuals carrying the isoleucine allele had an 18% (95% confidence interval 4-30%, P=0.015) lower risk of obesity compared with non-carriers. There was no heterogeneity among studies and no apparent publication bias.
This study confirms that the V103I polymorphism protects against human obesity at a population level. As such it provides proof of principle that specific gene variants may, at least in part, explain susceptibility and resistance to common forms of human obesity. A better understanding of the mechanisms underlying this association will help determine whether changes in MC4R activity have therapeutic potential.
先前的研究表明，黑皮质素4受体（MC4R）基因中的一个变体在预防普通肥胖方面很重要。然而，需要更大规模的研究来证实这种关系。
我们在三项基于英国人群的队列研究中评估了MC4R基因V103I多态性与肥胖之间的关联，共计8304人。我们还对相关研究进行了荟萃分析，涉及10975例病例和18588例对照，以便将我们的研究结果置于相应背景中。
在对所有研究的分析中，与非携带者相比，携带异亮氨酸等位基因的个体肥胖风险降低了18%（95%置信区间4%-30%，P=0.015）。研究之间没有异质性，也没有明显的发表偏倚。
本研究证实，V103I多态性在人群水平上可预防人类肥胖。因此，它提供了原理证明，即特定的基因变体可能至少部分地解释人类对常见肥胖形式的易感性和抗性。更好地理解这种关联背后的机制将有助于确定MC4R活性的变化是否具有治疗潜力。
