Scott E M, Carter A M, Grant P J
LIGHT Laboratories, Academic Unit of Molecular Vascular Medicine, Leeds Institute of Genetics Health and Therapeutics, University of Leeds, Leeds, UK.
Int J Obes (Lond). 2008 Apr;32(4):658-62. doi: 10.1038/sj.ijo.0803778. Epub 2007 Dec 11.
Accumulating evidence raises the hypothesis that dysregulation of intrinsic clock mechanisms are involved in the development of the metabolic syndrome, type 2 diabetes mellitus and cardiovascular disease. The aim of the present study was to investigate the relationship between three known common polymorphisms in the Clock gene and features of the metabolic syndrome in man.
Genotype and haplotype analysis was carried out in a cohort of 537 individuals from 89 families characterized for inflammatory, atherothrombotic and metabolic risk associated with insulin resistance.
Heritability of the metabolic syndrome, defined according to International Diabetes Federation criteria, was 0.40. Haplotype analysis indicated three common haplotypes: CAT, TGT and CGC (rs4864548-rs3736544-rs1801260) with frequencies of 31, 33 and 28%, respectively. The CGC haplotype was less prevalent in subjects with the metabolic syndrome (P=0.0015) and was associated with lower waist circumference (P=0.007), lower hip circumference (P=0.023), lower body mass index (P=0.043) and lower leptin levels (P=0.028). The CAT haplotype was significantly associated with the presence of the metabolic syndrome (P=0.020).
These findings suggest that the Clock gene CGC haplotype may be protective for the development of obesity and support the hypothesis that genetic variation in the Clock gene may play a role in the development of the metabolic syndrome, type 2 diabetes and cardiovascular disease.
越来越多的证据提出了一种假说，即内在生物钟机制失调与代谢综合征、2型糖尿病和心血管疾病的发生有关。本研究的目的是调查生物钟基因中三种已知常见多态性与人代谢综合征特征之间的关系。
对来自89个家庭的537名个体进行了基因型和单倍型分析，这些家庭具有与胰岛素抵抗相关的炎症、动脉粥样硬化血栓形成和代谢风险特征。
根据国际糖尿病联盟标准定义的代谢综合征遗传度为0.40。单倍型分析表明存在三种常见单倍型：CAT、TGT和CGC（rs4864548-rs3736544-rs1801260），频率分别为31%、33%和28%。CGC单倍型在代谢综合征患者中不太常见（P=0.0015），并与较低的腰围（P=0.007）、较低的臀围（P=0.023）、较低的体重指数（P=0.043）和较低的瘦素水平（P=0.028）相关。CAT单倍型与代谢综合征的存在显著相关（P=0.020）。
这些发现表明，生物钟基因CGC单倍型可能对肥胖的发生具有保护作用，并支持生物钟基因的遗传变异可能在代谢综合征、2型糖尿病和心血管疾病的发生中起作用这一假说。
