期刊
DIABETES
卷 57, 期 11, 页码 3145-3151出版社
AMER DIABETES ASSOC
DOI: 10.2337/db08-0006
关键词
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资金
- American Heart Association
- Boston Obesity Nutrition Research Center [DK46200]
- National Institutes of Health [DK-58845, CA-87969]
OBJECTIVE-To examine the longitudinal association of fat, mass- and obesity-associated (FTO) variant with obesity, circulating adipokine levels, and FTO expression in various materials from human and mouse. RESEARCH DESIGN AND METHODS-We genotyped rs9939609 in 2,287 men and 3,520 women from two prospective cohorts. Plasma adiponectin and leptin were measured in a subset of diabetic men (n = 854) and women (n = 987). Expression of FTO was tested in adipocytes from db/db mice and mouse macrophages. RESULTS-We observed a trend toward decreasing associations between rs9939609 and BMI at older age ( >= 65 years) in men, whereas the associations were constant across different age groups in women. In addition, the single nucleotide polymorphism (SNP) rs9939609 was associated with lower plasma adiponectin (log[e]- means, 1.82 +/- 0.04, 1.73 +/- 0.03, and 1.68 +/- 0.05 for TT, TA, and AA genotypes, respectively; P for trend 0.02) and leptin (log[e]- means, 3.56 +/- 0.04, 3.63 +/- 0.04, and 3.70 +/- 0.06; P for trend = 0.06) in diabetic women. Adjustment for BMI attenuated the associations. FTO gene was universally expressed in human and mice tissues, including adipocytes. In an ancillary study of adipocytes from db/db mice, FTO expression was similar to 50% lower than in those from wild-type mice. CONCLUSIONS-The association between FTO SNP rs9939609 and obesity risk may decline at older age. The variant affects circulating adiponectin and leptin levels through the changes in BMI. In addition, the expression of FTO gene was reduced in adipocytes from db/db mice. Diabetes 57:3145-3151, 2008
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