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Arterioscler Thromb Vasc Biol. 2010 Feb;30(2):327-32. doi: 10.1161/ATVBAHA.109.196196. Epub 2009 Nov 12.

Obesity genotype score and cardiovascular risk in women with type 2 diabetes mellitus.

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  • 1Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.



To investigate the associations between obesity-predisposing genetic variants, cardiovascular biomarkers, and cardiovascular disease (CVD) risk in women with preexisting type 2 diabetes mellitus.


We genotyped polymorphisms at nine established obesity loci in 1,395 women with diabetes from the Nurses' Health Study: 449 women developed CVD, and 946 women did not develop CVD. A genetic risk score (GRS) was derived by summing risk alleles for each individual. Four polymorphisms (rs9939609 [FTO], rs11084753 [KCTD15], rs10838738 [MTCH2], and rs10938397 [GNPDA2]) showed nominally significant associations with CVD. The GRS combining all obesity loci was linearly related to CVD risk (P = 0.013 for trend). The odds ratio was 1.08 per risk allele (95% confidence interval, 1.02-1.15; P = 0.01) after adjustment for body mass index and other conventional risk factors. Women with the highest quartile of GRS had 53% (95% confidence interval, 6%-122%) increased CVD risk, compared with those in the lowest quartile of GRS (P = 0.024). In addition, a higher GRS was associated with lower adiponectin levels (P = 0.02). Further adjustment for body mass index and other covariates did not change the association (P = 0.006). A higher GRS was also correlated with lower levels of high-density lipoprotein (P = 0.01).


Obesity-predisposing variants may jointly affect CVD risk among women with diabetes.

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