Abstract 1264: Obesity Genotype Score and Cardiovascular Risk in Women With Type 2 Diabetes
OBJECTIVES To investigate the associations between obesity-predisposing genetic variants, cardiovascular biomarkers and cardiovascular disease (CVD) in women with preexisting type 2 diabetes.
RESEARCH DESIGN AND METHODS We genotyped polymorphisms at nine loci in 1,395 women with diabetes from the Nurses’ Health Study; 449 of these women developed CVD and 946 did not. A genetic risk score (GRS) was derived by summing risk alleles for each individual.
RESULTS Four polymorphisms, rs9939609 (FTO), rs11084753 (KCTD15), rs10838738 (MTCH2), and rs10938397 (GNPDA2), showed nominally significant associations with CVD risk. The mean (range) GRS combining all obesity loci was 6.4(1–12) among subjects in whom CVD developed and 6.1 (1–14) among those in whom CVD did not develop (P=0.02). The GRS was linearly related to CVD risk (P for trend=0.013). The odds ratio (OR) for CVD was 1.09 per risk allele (95% confidence interval [CI]: 1.02–1.15; P=0.008) after adjustment for body mass index (BMI) and other conventional risk factors. Women whose GRS in the highest quartile had 53% (6%–122%) increased risk of CVD, compared with those in the lowest quartile (P=0.024). In addition, higher GRS was associated with lower adiponectin levels (P=0.02). Further adjustment for BMI and other covariates did not change the association (P=0.006). Higher GRS was also correlated with lower levels of high-density lipoprotein (HDL) (P=0.01). Adjustment for BMI attenuated the association (P=0.05).
CONCLUSIONS Obesity-predisposing variants may jointly affect CVD risk among women with diabetes. These associations may partly be mediated by the changes in adiponectin and lipids.
This research has received full or partial funding support from the American Heart Association, Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).