Li Huaixing, Wu Ying, Loos Ruth J F, Hu Frank B, Liu Yong, Wang Jing, Yu Zhijie, Lin Xu
Key Laboratory of Systems Biology, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences and Graduate School of the Chinese Academy of Sciences, Shanghai, China.
Diabetes. 2008 Jan;57(1):264-8. doi: 10.2337/db07-1130. Epub 2007 Oct 24.
Recently, genome-wide association studies have provided evidence that several common variants within the fat mass-and obesity-associated (FTO) gene were significantly associated with obesity in populations of European origin. However, their effects in other ethnic populations remain to be elucidated.
In this study, we examined the association between three FTO variants (rs8050136, rs9939609, and rs9930506) and obesity and related traits in a population-based study of 3,210 unrelated Chinese Han subjects from Shanghai and Beijing. In secondary analyses, we also tested for association with type 2 diabetes and related traits. Logistics regression and generalized linear models were used to test for additive and dominant effects of the risk alleles.
The minor allele frequencies of rs8050136, rs9939609, and rs9930506 in our population (0.12, 0.12, and 0.20, respectively) were substantially lower than those observed for populations of European descent (e.g., for CEU population of HapMap: 0.45, 0.48, and 0.45, respectively). Despite our study being sufficiently powered to detect effects similar to those previously reported, none of the FTO SNPs were found to be associated with obesity, overweight, BMI, waist circumference, or body fat percentage. In addition, none of the SNPs exhibited significant associations with fasting levels of plasma glucose, A1C, insulin, or beta-cell function (estimated via homeostasis model assessment) under either an additive or a dominant model in the quantitative trait analyses. Analyses stratified by sex or geographical region did not change these observations.
Our data do not support that the FTO common variants are major contributors of obesity or type 2 diabetes in the Chinese Han population.
最近，全基因组关联研究已提供证据表明，脂肪量与肥胖相关基因（FTO）内的几个常见变异与欧洲裔人群的肥胖显著相关。然而，它们在其他种族人群中的作用仍有待阐明。
在本研究中，我们在一项基于人群的研究中，对来自上海和北京的3210名无亲缘关系的中国汉族受试者，检测了三个FTO变异（rs8050136、rs9939609和rs9930506）与肥胖及相关性状之间的关联。在二次分析中，我们还检测了与2型糖尿病及相关性状的关联。采用逻辑回归和广义线性模型来检测风险等位基因的加性和显性效应。
我们研究人群中rs8050136、rs9939609和rs9930506的次要等位基因频率（分别为0.12、0.12和0.20）显著低于欧洲血统人群中观察到的频率（例如，国际人类基因组单体型图计划中的CEU人群：分别为0.45、0.48和0.45）。尽管我们的研究有足够的效能来检测与先前报道相似的效应，但未发现任何FTO单核苷酸多态性与肥胖、超重、体重指数、腰围或体脂百分比相关。此外，在定量性状分析中，无论是加性模型还是显性模型下，均未发现任何单核苷酸多态性与空腹血糖水平、糖化血红蛋白、胰岛素或β细胞功能（通过稳态模型评估估算）存在显著关联。按性别或地理区域分层的分析并未改变这些观察结果。
我们的数据不支持FTO常见变异是中国汉族人群肥胖或2型糖尿病的主要促成因素。
