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FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women.

ABSTRACT: The FTO gene was recently identified as a susceptibility locus for both obesity and type 2 diabetes by whole-genome association analyses of several European populations. We tested for an association between FTO risk alleles and obesity and diabetes in a well-characterized multiethnic cohort of postmenopausal women in the United States. We genotyped two most significantly associated single-nucleotide polymorphisms (SNPs) (rs9939609 and rs8050136) in intron 1 of FTO gene in a nested case-control study of 1,517 diabetes cases and 2,123 controls from the Women's Health Initiative-Observational Study (WHI-OS). The allelic frequencies of either rs9939609 or rs8050136 differed widely across four ethnic groups. The frequency of the rare allele A of rs9939609 among controls was much lower in Asians/Pacific Islanders (17%) than in blacks (45%), whites (40%), and Hispanics (31%). We found significant associations of rs9939609 with BMI and waist circumference in white and Hispanic women, but not among black and Asian/Pacific Islander women. On average, each copy of the risk-allele A at rs9939609 was significantly associated with 0.45 kg/m(2) increase in BMI (95% confidence interval (CI): 0.16-0.74; P = 0.004) and 0.97 cm increase in waist circumference (95% CI: 0.21-0.65; P = 0.0002). Similar results were observed for rs8050136. However, we found no significant genetic associations with diabetes risk, either within the full study sample or in any ethnic group. In conclusion, common genetic variants in the intron 1 of FTO gene may confer a modest susceptibility to obesity in an ethnicity-specific manner, but may be unlikely to contribute to a clinically significant diabetes risk.

SUBMITTER: Song Y

PROVIDER: S-EPMC2732012 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women.

Song Yiqing Y You Nai-Chieh NC Hsu Yi-Hsiang YH Howard Barbara V BV Langer Robert D RD Manson Joann E JE Nathan Lauren L Niu Tianhua T F Tinker Lesley L Liu Simin S

Obesity (Silver Spring, Md.) 20080911 11

The FTO gene was recently identified as a susceptibility locus for both obesity and type 2 diabetes by whole-genome association analyses of several European populations. We tested for an association between FTO risk alleles and obesity and diabetes in a well-characterized multiethnic cohort of postmenopausal women in the United States. We genotyped two most significantly associated single-nucleotide polymorphisms (SNPs) (rs9939609 and rs8050136) in intron 1 of FTO gene in a nested case-control s ...[more]

PMID: 18787525

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Project description:Association of body mass index and hip fracture has been controversial. In this study, women with lowest and highest body weight had the highest fracture incidence. A 25-year follow-up indicated that obesity associates with early hip fracture risk and suggested increasing trend in normal-weight women at a later stage.IntroductionObesity is a pandemic health issue. Its association with hip fracture risk remains controversial. We studied the long-term relationship of body mass index and hip fracture incidence in postmenopausal women.MethodsThe cohort of 12,715 Finnish women born in 1932-1941 was followed for 25 years, covering ages from 58 up to 83. Fractures and deaths were obtained from national registries. Women were investigated in deciles of BMI as well as in WHO weight categories (normal, overweight, or obese). The follow-up analysis was carried out in two age strata as "early" (58-70 years) and "late" (> 70 years). Body weight information was updated accordingly. Femoral neck BMD was recorded for a subsample (n = 3163). Altogether, 427 hip fractures were observed.ResultsA higher risk of early hip fracture was observed in obese and normal-weight compared with overweight women with hazard ratios (HRs) of 2.3 ((95% CI) 1.4-3.7) and 2.0 (1.3-3.1) while no difference was observed in late hip fracture risk between the three WHO categories (log rank p = 0.14). All-cause mortality during the follow-up was 19.3%. Compared with normal weight women, the obese women had a higher risk of death with an HR of 1.6 (1.4-1.8) and higher baseline BMD (p < 0.001). Faster bone loss was observed in the obese compared with other women (p < 0.001).ConclusionObesity associates with earlier hip fracture and higher postfracture mortality. The obese women with low BMD have clearly the highest risk of hip fracture. This combination increases hip fracture risk more than either of the factors alone. After 75 years of age, risk appears to increase more in normal weight women, but this trend is in need of further confirmation.

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FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women.

Publications

FTO polymorphisms are associated with obesity but not diabetes risk in postmenopausal women.

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