College of Medical and Dental Sciences, University of Birmingham, Birmingham, UK.
Diabet Med. 2011 Jun;28(6):673-80. doi: 10.1111/j.1464-5491.2011.03257.x.
A common variant, rs9939609, in the FTO (fat mass and obesity) gene is associated with adiposity in Europeans, explaining its relationship with diabetes. However, data are inconsistent in South Asians. Our aim was to investigate the association of the FTO rs9939609 variant with obesity, obesity-related traits and Type 2 diabetes in South Asian individuals, and to use meta-analyses to attempt to clarify to what extent BMI influences the association of FTO variants with diabetes in South Asians.
We analysed rs9939609 in two studies of Pakistani individuals: 1666 adults aged ≥40 years from the Karachi population-based Control of Blood Pressure and Risk Attenuation (COBRA) study and 2745 individuals of Punjabi ancestry who were part of a Type 2 diabetes case-control study (UK Asian Diabetes Study/Diabetes Genetics in Pakistan; UKADS/DGP). The main outcomes were BMI, waist circumference and diabetes. Regression analyses were performed to determine associations between FTO alleles and outcomes. Summary estimates were combined in a meta-analysis of 8091 South Asian individuals (3919 patients with Type 2 diabetes and 4172 control subjects), including those from two previous studies.
In the 4411 Pakistani individuals from this study, the age-, sex- and diabetes-adjusted association of FTO variant rs9939609 with BMI was 0.45 (95%CI 0.24-0.67) kg/m(2) per A-allele (P=3.0 × 10(-5) ) and with waist circumference was 0.88 (95% CI 0.36-1.41) cm per A-allele (P=0.001). The A-allele (30% frequency) was also significantly associated with Type 2 diabetes [per A-allele odds ratio (95%CI) 1.18 (1.07-1.30); P=0.0009]. A meta-analysis of four South Asian studies with 8091 subjects showed that the FTO A-allele predisposes to Type 2 diabetes [1.22 (95%CI 1.14-1.31); P=1.07 × 10(-8) ] even after adjusting for BMI [1.18 (95%CI 1.10-1.27); P=1.02 × 10(-5) ] or waist circumference [1.18 (95%CI 1.10-1.27); P=3.97 × 10(-5) ].
The strong association between FTO genotype and BMI and waist circumference in South Asians is similar to that observed in Europeans. In contrast, the strong association of FTO genotype with diabetes is only partly accounted for by BMI.
FTO（肥胖与肥胖相关基因）基因中的常见变异 rs9939609 与欧洲人的肥胖有关，可解释其与糖尿病的关系。然而，南亚的数据并不一致。我们的目的是研究 FTO rs9939609 变异与南亚个体肥胖、肥胖相关特征和 2 型糖尿病的关系，并使用荟萃分析来阐明 BMI 在多大程度上影响 FTO 变异与南亚人糖尿病的关联。
我们分析了来自巴基斯坦个体的两项研究中的 rs9939609：来自卡拉奇人群为基础的血压控制和风险衰减（COBRA）研究的 1666 名年龄≥40 岁的成年人和 2745 名旁遮普血统的个体，他们是 2 型糖尿病病例对照研究（英国亚洲糖尿病研究/巴基斯坦糖尿病遗传学；UKADS/DGP）的一部分。主要结局是 BMI、腰围和糖尿病。回归分析用于确定 FTO 等位基因与结局之间的关系。在包括来自两项先前研究的 8091 名南亚个体（3919 名 2 型糖尿病患者和 4172 名对照者）的荟萃分析中合并了汇总估计值。
在这项研究中的 4411 名巴基斯坦个体中，FTO 变体 rs9939609 与 BMI 的年龄、性别和糖尿病调整关联为 0.45（95%CI 0.24-0.67）kg/m(2) / A-等位基因（P=3.0×10(-5) ），与腰围的关联为 0.88（95%CI 0.36-1.41）cm/A-等位基因（P=0.001）。A-等位基因（30%的频率）也与 2 型糖尿病显著相关[每 A-等位基因比值比（95%CI）1.18（1.07-1.30）；P=0.0009]。对四项包含 8091 名受试者的南亚研究进行的荟萃分析显示，即使在调整 BMI[1.22（95%CI 1.14-1.31）；P=1.07×10(-8) ]或腰围[1.22（95%CI 1.14-1.31）；P=1.02×10(-5) ]后，FTO A-等位基因也易患 2 型糖尿病[1.18（95%CI 1.10-1.27）；P=1.02×10(-5) ]。
FTO 基因型与南亚人 BMI 和腰围之间的强烈关联与在欧洲人观察到的相似。相比之下，FTO 基因型与糖尿病的强烈关联仅部分归因于 BMI。
