一种常见变异与儿童MC4R基因转录水平与肥胖相关：IDEFICS研究。
A Common Variant and the Transcript Levels of MC4R Gene Are Associated With Adiposity in Children: The IDEFICS Study.
作者信息
Lauria Fabio, Siani Alfonso, Picó Catalina, Ahrens Wolfgang, Bammann Karin, De Henauw Stefaan, Foraita Ronja, Iacoviello Licia, Kourides Yiannis, Marild Staffan, Molnar Denes, Moreno Luis A, Pitsiladis Yannis, Sánchez Juana, Veidebaum Toomas, Wang Guan, Russo Paola
机构信息
Unit of Epidemiology and Population Genetics (F.L., A.S., P.R.), Institute of Food Sciences, National Research Council, I-83100 Avellino, Italy; Laboratory of Molecular Biology, Nutrition, and Biotechnology (Nutrigenomics) (C.P., J.S.), University of the Balearic Islands and Centro de Investigación Biomédica en Red Fisiopatología de la Obesidad y Nutrición, Palma de 07122 Mallorca, Spain; Leibniz Institute for Prevention Research and Epidemiology-BIPS (W.A., K.B., R.F.), and Faculty of Mathematics and Computer Science (W.A.), University of Bremen, and Institute for Public Health and Nursing Research (K.B.), Faculty for Human and Health Sciences, University Bremen, D-28359 Bremen, Germany; Department of Public Health (S.D.H.), Ghent University, 9000 Ghent, Belgium; Department of Epidemiology and Prevention (L.I.), Instituto di Ricovero e Cura a Carattere Scientifico Istituto Neurologico Mediterraneo NEUROMED, 86077 Pozzilli, Italy; Research and Education Institute of Child Health (Y.K.), 2015 Strovolos, Cyprus; Department of Pediatrics (S.M.), Institute of Clinical Sciences, The Queen Silvia Children's Hospital, The Sahlgrenska Academy at the University of Gothenburg, SE-413 45 Göteborg, Sweden; Department of Paediatrics (D.M.), Medical Faculty, University of Pécs, 7622 Pécs, Hungary; GENUD (Growth, Exercise, Nutrition and Development) research group, Facultad de Ciencias de la Salud, Instituto Agroalimentario de Aragón (IA2), Instituto de Investigación Sanitaria Aragón (IIS Aragón), Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (CIBERObn), (L.A.M.) Universidad de Zaragoza, 50009 Zaragoza (Spain) FIMS Reference Collaborating Centre of Sports Medicine for Anti-Doping Research (Y.P., G.W.), University of Brighton, Eastbourne BN2 4AT, United Kingdom; and National Institute for Health Development (T.V.), 11619 Tallinn, Estonia.
出版信息
J Clin Endocrinol Metab. 2016 Nov;101(11):4229-4236. doi: 10.1210/jc.2016-1992. Epub 2016 Sep 1.
CONTEXT
The melanocortin-4 receptor gene (MC4R) plays a pivotal role in the regulation of body fat and food and energy intake.
OBJECTIVES
The objectives of the study were as follows: 1) to evaluate the association of variants rs17782313 and rs17700633 near the coding region of MC4R and 2) to evaluate the association of the transcript levels of MC4R with adiposity indices and percentage of energy from fat, carbohydrates, and protein in children.
DESIGN
The Identification and Prevention of Dietary- and Lifestyle-Induced Health Effects in Children and Infants (IDEFICS) cohort was used, with examinations at baseline (T0) and after 2 years (T1).
SETTING AND PARTICIPANTS
A total of 16 228 schoolchildren (2-9 y) from eight European countries participated in the study. A random sample of 4381 children genotyped for MC4R variants and a subsample of 410 children with MC4R expression data in peripheral blood cells (PBCs) were included in the analyses.
MAIN OUTCOME MEASURES
Anthropometric measures and energy intake (total and from fat, carbohydrates, and protein) served as outcomes for adiposity status and for dietary behavior, respectively.
RESULTS
At T0, the C allele of rs17782313 (minor frequency allele 23%) was significantly associated with higher values of adiposity indices (all P < .001). No association was found between rs17700633 (minor frequency allele 28%) and the variables under study. At T1, the C allele of rs17782313 was associated with a significantly higher increase in the adiposity indices over time (all P < .05). The MC4R expression levels in PBCs were inversely associated with body fat and energy intake from carbohydrates and directly with energy from fat (all P ≤ .05) but were not influenced by variants rs17782313 and rs17700633.
CONCLUSIONS
The common variant rs17782313 near MC4R was cross-sectionally and longitudinally associated with body mass index and measures of body fatness in children aged 2-9 years. We showed, for the first time in humans, that MC4R expression levels in PBCs are related to body fat distribution and percentage of energy intake from carbohydrates and fat.
背景
黑皮质素-4受体基因（MC4R）在身体脂肪以及食物和能量摄入的调节中起关键作用。
目的
本研究的目的如下：1）评估MC4R编码区附近的rs17782313和rs17700633变异的相关性；2）评估儿童中MC4R转录水平与肥胖指数以及来自脂肪、碳水化合物和蛋白质的能量百分比之间的相关性。
设计
采用儿童和婴儿饮食及生活方式诱导健康效应的识别与预防（IDEFICS）队列研究，在基线（T0）和2年后（T1）进行检查。
地点和参与者
来自八个欧洲国家的总共16228名学童（2 - 9岁）参与了该研究。分析纳入了4381名对MC4R变异进行基因分型的儿童随机样本以及410名在外周血细胞（PBC）中有MC4R表达数据的儿童子样本。
主要观察指标
人体测量指标和能量摄入（总量以及来自脂肪、碳水化合物和蛋白质的量）分别作为肥胖状态和饮食行为的观察指标。
结果
在T0时，rs17782313的C等位基因（次要频率等位基因23%）与较高的肥胖指数值显著相关（所有P < 0.001）。未发现rs17700633（次要频率等位基因28%）与所研究变量之间存在相关性。在T1时，rs17782313的C等位基因与肥胖指数随时间的显著更高增加相关（所有P < 0.05）。PBC中MC4R的表达水平与体脂以及碳水化合物的能量摄入呈负相关，与脂肪能量呈正相关（所有P≤0.05），但不受rs17782313和rs17700633变异的影响。
结论
MC4R附近的常见变异rs17782313与2 - 9岁儿童的体重指数和体脂测量值在横断面和纵向上均相关。我们首次在人类中表明，PBC中MC4R的表达水平与体脂分布以及碳水化合物和脂肪的能量摄入百分比有关。
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