Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People's Republic of China.
Diabetologia. 2012 Apr;55(4):981-95. doi: 10.1007/s00125-011-2370-7. Epub 2011 Nov 23.
AIMS/HYPOTHESIS: FTO harbours the strongest known obesity-susceptibility locus in Europeans. While there is growing evidence for a role for FTO in obesity risk in Asians, its association with type 2 diabetes, independently of BMI, remains inconsistent. To test whether there is an association of the FTO locus with obesity and type 2 diabetes, we conducted a meta-analysis of 32 populations including 96,551 East and South Asians.
All studies published on the association between FTO-rs9939609 (or proxy [r (2) > 0.98]) and BMI, obesity or type 2 diabetes in East or South Asians were invited. Each study group analysed their data according to a standardised analysis plan. Association with type 2 diabetes was also adjusted for BMI. Random-effects meta-analyses were performed to pool all effect sizes.
The FTO-rs9939609 minor allele increased risk of obesity by 1.25-fold/allele (p = 9.0 × 10(-19)), overweight by 1.13-fold/allele (p = 1.0 × 10(-11)) and type 2 diabetes by 1.15-fold/allele (p = 5.5 × 10(-8)). The association with type 2 diabetes was attenuated after adjustment for BMI (OR 1.10-fold/allele, p = 6.6 × 10(-5)). The FTO-rs9939609 minor allele increased BMI by 0.26 kg/m(2) per allele (p = 2.8 × 10(-17)), WHR by 0.003/allele (p = 1.2 × 10(-6)), and body fat percentage by 0.31%/allele (p = 0.0005). Associations were similar using dominant models. While the minor allele is less common in East Asians (12-20%) than South Asians (30-33%), the effect of FTO variation on obesity-related traits and type 2 diabetes was similar in the two populations.
CONCLUSIONS/INTERPRETATION: FTO is associated with increased risk of obesity and type 2 diabetes, with effect sizes similar in East and South Asians and similar to those observed in Europeans. Furthermore, FTO is also associated with type 2 diabetes independently of BMI.
目的/假设：FTO 是欧洲人群中已知的最强肥胖易感基因座。虽然越来越多的证据表明 FTO 与亚洲人群的肥胖风险有关，但它与 2 型糖尿病的关联，与 BMI 无关，仍然不一致。为了检验 FTO 基因座与肥胖和 2 型糖尿病之间是否存在关联，我们对包括 96551 名东亚和南亚人在内的 32 个人群进行了荟萃分析。
我们邀请了所有已发表的关于 FTO-rs9939609（或其代理物[r (2) > 0.98]）与东亚或南亚人群 BMI、肥胖或 2 型糖尿病之间关联的研究。每个研究组都根据标准化分析方案分析了他们的数据。对 2 型糖尿病的关联也进行了 BMI 调整。采用随机效应荟萃分析汇总所有效应大小。
FTO-rs9939609 次要等位基因使肥胖的风险增加 1.25 倍/等位基因（p = 9.0 × 10(-19)），超重增加 1.13 倍/等位基因（p = 1.0 × 10(-11)），2 型糖尿病增加 1.15 倍/等位基因（p = 5.5 × 10(-8)）。在调整 BMI 后，与 2 型糖尿病的关联减弱（OR 1.10 倍/等位基因，p = 6.6 × 10(-5)）。FTO-rs9939609 次要等位基因使 BMI 增加 0.26 公斤/平方米/等位基因（p = 2.8 × 10(-17)），WHR 增加 0.003/等位基因（p = 1.2 × 10(-6)），体脂肪百分比增加 0.31%/等位基因（p = 0.0005）。显性模型的结果相似。虽然东亚人群（12-20%）中 FTO 等位基因的频率低于南亚人群（30-33%），但 FTO 变异对肥胖相关特征和 2 型糖尿病的影响在两个人群中是相似的。
结论/解释：FTO 与肥胖和 2 型糖尿病的风险增加有关，其效应大小在东亚人和南亚人之间相似，与欧洲人观察到的结果相似。此外，FTO 与 2 型糖尿病的关联也与 BMI 无关。
