Common Variation in the Fat Mass and Obesity-Associated (FTO) Gene Confers Risk of Obesity and Modulates BMI in the Chinese Population

Author:

Chang Yi-Cheng1,Liu Pi-Hua2,Lee Wei-Jei3,Chang Tien-Jyun4,Jiang Yi-Der4,Li Hung-Yuan4,Kuo Shan-Shan4,Lee Kuang-Chin4,Chuang Lee-Ming45

Affiliation:

1. Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan

2. Institute of Epidemiology, College of Public Health, National Taiwan University, Taipei, Taiwan

3. Department of Surgery, Ming-Sheng General Hospital, Taoyuan, Taiwan

4. Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

5. Graduate Institute of Clinical Medicine, National Taiwan University Medical College, Taipei, Taiwan

Abstract

OBJECTIVE— Genetic variants in the fat mass and obesity-associated (FTO) gene have been linked with obesity and type 2 diabetes in European populations. We aimed to test the role of FTO genetic variants in obesity and type 2 diabetes in the Chinese population. RESEARCH DESIGN AND METHODS— We genotyped 19 single-nucleotide polymorphisms (SNPs) spanning from the 3′ end of the neighboring RPGRIP1L gene to the 5′ flanking region of the FTO gene. We analyzed their associations with obesity (638 case and 1,610 control subjects), type 2 diabetes (759 case and 784 control subjects), and obesity-related traits in nondiabetic subjects. RESULTS— Among the 19 SNPs, the rs9939609 A allele was strongly associated with obesity (P = 7.0 × 10−4) and BMI (P = 0.0024) in the Chinese population. The odds ratio for obesity was 2.60 (95% CI 1.24–5.46) (P = 0.011) for the AA genotype and 1.32 (1.05–1.66) (P = 0.018) for the AT genotype compared with the TT genotype. Each additional copy of the rs9936609 A allele was associated with a BMI increase of ∼0.37 kg/m2. The rs9939609 A allele was substantially less common in the Chinese population than in the European population (12.6 vs. 45%). We did not find significant associations of the 19 SNPs with type 2 diabetes or other obesity-related traits. CONCLUSIONS— Genetic variation in the FTO gene is strongly associated with obesity and BMI in the Chinese population. The risk variant is less common in the Chinese population, but its effect size on BMI is comparable with that in the European population.

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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