Unit of Genetic Epidemiology and Bioinformatics, Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Georgia Prevention Institute, Department of Pediatrics, Medical College of Georgia, Augusta, GA, USA.
J Pediatr. 2010 Apr;156(4):598-605.e1. doi: 10.1016/j.jpeds.2009.10.037. Epub 2010 Jan 12.
Recent genome-wide association studies found common variants near the melanocortin 4 receptor gene associated with obesity. This study aimed to assess the influence of the identified single nucleotide polymorphisms rs17782313 and rs17700633 on general and visceral adiposity in European- and African-American youth.
In 1890 youth (49.1% European-American, 45.6% male, mean age 16.7 years), we examined the associations of the rs17782313 and rs17700633 with anthropometry, percent body fat, visceral adipose tissue, and subcutaneous abdominal adipose tissue. Interaction of the single nucleotide polymorphisms with ethnicity or sex was investigated and haplotype analyses conducted.
Rs17782313 was significantly associated with weight (P = .02) and waist circumference (P = .03) in all subjects and with body mass index (P = .002) in females. In females rs17700633 was significantly associated with percent body fat (P = .001), visceral adipose tissue (P < .001), and subcutaneous abdominal adipose tissue (P < .001). Rs17700633 was significantly associated with fasting insulin and homeostasis model assessment, but the significance attenuated after adjustment for percent body fat. These findings were confirmed by haplotype analysis. No significant interactions of the variants with ethnicity were found for any of these phenotypes.
The relatively large effect of these common variants near melanocortin 4 receptor on general and visceral adiposity in childhood, especially in girls, could prove helpful in elucidating the molecular mechanisms underlying the development of obesity in early life.
最近的全基因组关联研究发现，黑皮质素 4 受体基因附近的常见变异与肥胖有关。本研究旨在评估鉴定的单核苷酸多态性 rs17782313 和 rs17700633 对欧洲裔和非裔美国青少年一般和内脏肥胖的影响。
在 1890 名青少年（49.1%为欧洲裔，45.6%为男性，平均年龄 16.7 岁）中，我们研究了 rs17782313 和 rs17700633 与人体测量学、体脂百分比、内脏脂肪组织和腹部皮下脂肪组织的关联。研究了单核苷酸多态性与种族或性别之间的相互作用，并进行了单倍型分析。
rs17782313 在所有受试者中与体重（P =.02）和腰围（P =.03）显著相关，在女性中与体重指数（P =.002）显著相关。在女性中，rs17700633 与体脂百分比（P =.001）、内脏脂肪组织（P <.001）和腹部皮下脂肪组织（P <.001）显著相关。rs17700633 与空腹胰岛素和稳态模型评估显著相关，但在调整体脂百分比后，其显著性减弱。这些发现通过单倍型分析得到了证实。对于这些表型，没有发现这些变体与种族之间存在显著的相互作用。
这些位于黑皮质素 4 受体附近的常见变异对儿童期一般和内脏肥胖的影响相对较大，尤其是在女孩中，这可能有助于阐明生命早期肥胖发展的分子机制。
