Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, USA.
Obesity (Silver Spring). 2012 Sep;20(9):1902-8. doi: 10.1038/oby.2011.238. Epub 2011 Jul 28.
Recent studies have identified common genetic variants that are unequivocally associated with central adiposity, BMI, and/or fasting plasma glucose among individuals of European descent. Our objective was to evaluate these associations in a population of Asian-Indians. We examined 16 single-nucleotide polymorphisms (SNPs) from loci previously linked to waist circumference, BMI, or fasting glucose in 1,129 Asian-Indians from New Delhi and Trivandrum. Trained medical staff measured waist circumference, height, and weight. Fasting plasma glucose was measured from collected blood specimens. Genotype-phenotype associations were evaluated using linear regression, with adjustments for age, gender, religion, and study region. For gene-environment interaction tests, total physical activity (PA) during the past 7 days was assessed by the International Physical Activity Questionnaire (IPAQ). The T allele at the FTO rs3751812 locus was associated with increased waist circumference (per allele effect of +1.58 cm, P(trend) = 0.0015) after Bonferroni adjustment for multiple testing (P(adj) = 0.04). We also found a nominally statistically significant FTO-PA interaction (P(interaction) = 0.008). Among participants with <81 metabolic equivalent (MET)-h/wk of PA, the rs3751812 variant was associated with increased waist size (+2.68 cm; 95% confidence interval (CI) = 1.24, 4.12), but not among those with 212+ MET-h/wk (-1.79 cm; 95% CI = -4.17, 0.58). No other variant had statistically significant associations, although statistical power was modest. In conclusion, we confirmed that an FTO variant associated with central adiposity in European populations is associated with central adiposity among Asian-Indians and corroborated prior reports indicating that high PA attenuates FTO-related genetic susceptibility to adiposity.
最近的研究已经确定了常见的遗传变异体，这些变异体在欧洲血统的个体中与中心性肥胖、BMI 和/或空腹血浆葡萄糖明确相关。我们的目标是评估这些关联在亚洲印度人群中的情况。我们研究了来自新德里和特里凡得琅的 1129 名亚洲印度人中的 16 个单核苷酸多态性（SNP），这些 SNP 位于以前与腰围、BMI 或空腹血糖相关的基因座。经过培训的医务人员测量了腰围、身高和体重。从收集的血液样本中测量空腹血浆葡萄糖。使用线性回归评估基因型-表型关联，调整年龄、性别、宗教和研究区域。对于基因-环境交互作用检验，使用国际体力活动问卷（IPAQ）评估过去 7 天的总体力活动（PA）。在经过多重测试的 Bonferroni 调整后，FTO rs3751812 基因座的 T 等位基因与腰围增加相关（每等位基因效应为+1.58cm，P(trend) = 0.0015）（P(adj) = 0.04）。我们还发现了一个名义上统计学显著的 FTO-PA 相互作用（P(interaction) = 0.008）。在 PA <81 代谢当量（MET）/wk 的参与者中，rs3751812 变体与腰围增大相关（+2.68cm；95%置信区间（CI）= 1.24, 4.12），但在 PA 212+MET-wk 的参与者中则不相关（-1.79cm；95%CI=-4.17, 0.58）。没有其他变体具有统计学意义的关联，尽管统计效力较小。总之，我们证实了与欧洲人群中心性肥胖相关的 FTO 变体与亚洲印度人群中的中心性肥胖相关，并证实了先前的报告表明，高 PA 可减弱 FTO 相关的肥胖遗传易感性。
