Heid Iris M, Vollmert Caren, Kronenberg Florian, Huth Cornelia, Ankerst Donna P, Luchner Andreas, Hinney Anke, Brönner Günter, Wichmann H-E, Illig Thomas, Döring Angela, Hebebrand Johannes
Institute of Epidemiology, GSF National Research Center for Environment and Health, Neuherberg, Germany.
Obesity (Silver Spring). 2008 Feb;16(2):369-76. doi: 10.1038/oby.2007.21.
Epidemiological studies showing an association between the melanocortin-4-receptor (MC4R) 103I variant (rs2229616) and decreased BMI are complemented by functional studies; these suggest a mechanism for appetite regulation and a linkage signal for physical activity and dietary intake for the region encompassing the MC4R. This study aims to provide epidemiological evidence for showing the association of this polymorphism with features of the metabolic syndrome and with parameters related to energy expenditure and dietary habits as potential mediators.
We analyzed this polymorphism in 7,888 adults of a population-based cross-sectional study applying regression-based statistical models.
Carriers of the MC4R 103I (3.7%) exhibited a significantly decreased waist circumference (-1.46 cm, P = 0.020), decreased glycosylated hemoglobin (HbA(1c)) (-0.09%, P = 0.040), and increased HDL-cholesterol (HDL-C) (+1.76 mg/dl, P = 0.056), but no change in blood pressure. The odds of having three or more components of the metabolic syndrome were substantially reduced among carriers of MC4R 103I (odds ratio (OR) = 0.46, P = 0.003). Controlling for BMI reduced the HbA(1c) and HDL-C association. Mediator analyses revealed a borderline association of MC4R 103I with carbohydrate intake (OR = 1.26, P = 0.059) possibly mediating association with leanness.
Our representative study of well-phenotyped Europeans is the first to describe the association of the MC4R V103I with the metabolic syndrome and with a nutrient-related phenotype. Our data support the idea that this polymorphism plays a role in appetite regulation that not only affects BMI, but also other features of the metabolic syndrome. It further establishes that the association of the MC4R V103I with obesity and related phenotypes is genuine.
流行病学研究显示黑皮质素-4-受体（MC4R）103I变异体（rs2229616）与体重指数（BMI）降低之间存在关联，功能研究对其进行了补充；这些研究提示了食欲调节机制以及包含MC4R区域的身体活动和饮食摄入的连锁信号。本研究旨在提供流行病学证据，以证明这种多态性与代谢综合征特征以及作为潜在中介因素的能量消耗和饮食习惯相关参数之间的关联。
我们在一项基于人群的横断面研究的7888名成年人中分析了这种多态性，应用基于回归的统计模型。
MC4R 103I的携带者（3.7%）腰围显著降低（-1.46厘米，P = 0.020），糖化血红蛋白（HbA1c）降低（-0.09%，P = 0.040），高密度脂蛋白胆固醇（HDL-C）升高（+1.76毫克/分升，P = 0.056），但血压无变化。MC4R 103I的携带者出现三种或更多代谢综合征组分的几率大幅降低（优势比（OR）= 0.46，P = 0.003）。校正BMI后降低了HbA1c与HDL-C的关联。中介分析显示MC4R 103I与碳水化合物摄入量存在临界关联（OR = 1.26，P = 0.059），可能介导了与消瘦的关联。
我们对表型良好的欧洲人的代表性研究首次描述了MC4R V103I与代谢综合征以及与营养相关表型之间的关联。我们的数据支持这样一种观点，即这种多态性在食欲调节中起作用，不仅影响BMI，还影响代谢综合征的其他特征。它进一步证实了MC4R V103I与肥胖及相关表型之间的关联是真实的。
