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Variants in the Fat Mass–and Obesity-Associated (FTO) Gene Are Not Associated With Obesity in a Chinese Han Population

¹ 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
² MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, U.K
³ Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts

Address correspondence and reprint requests to Dr. Xu Lin, Institute for Nutritional Sciences, Shanghai, 200031, China. E-mail: xlin{at}sibs.ac.cn

Key Words: HOMA-B, homeostasis model assessment of β-cell function • HOMA-S, homeostasis model assessment of insulin sensitivity • LD, linkage disequilibrium • MAF, minor allele frequency • SNP, single nucleotide polymorphism

OBJECTIVE— 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.

RESEARCH DESIGN AND METHODS— 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.

RESULTS— 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 β-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.

CONCLUSIONS— Our data do not support that the FTO common variants are major contributors of obesity or type 2 diabetes in the Chinese Han population.

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