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Genetic variant linked to elevated CHD risk in diabetics
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A research team has identified a genetic variant, rs10911021 on chromosome 1q25, that is strongly associated with risk for CHD in patients with type 2 diabetes.
Previous studies have suggested that genetic factors associated with elevated CHD risk are different in patients with diabetes compared with those without diabetes. Lu Qi, MD, PhD, of Harvard School of Public Health, and colleagues investigated the existence of genetic determinants of CHD that are found only in patients with diabetes.
The three-stage genome-wide analysis included participants with diabetes from five studies (n=1,517 with CHD; n=2,671 without CHD) and participants without diabetes from two studies (n=737 with CHD; n=1,637 without CHD).
The researchers tested 2,543,016 genetic variants for association with CHD. One, variant rs10911021 on chromosome 1q25, was consistently associated with CHD risk in patients with diabetes, with risk allele frequencies of 0.733 in patients with diabetes and CHD and 0.679 in patients with diabetes but no CHD (OR=1.36, 95% CI, 1.22-1.51).
However, in individuals without diabetes, the rs10911021 variant was not associated with CHD, with risk allele frequencies of 0.697 in individuals without diabetes but with CHD and 0.696 in individuals without diabetes or CHD (OR=0.99, 95% CI, 0.87-1.13).
Carriers of two copies of the variant had a 32% decrease in expression of the nearby GLUL gene in endothelial cells compared with individuals who carry no copies of the variant (P for trend=.0048). In addition, carriers of two copies of the variant had a lower ratio between plasma pyroglutamic acid and glutamic acid compared with those who carry no copies of the variant (P=.029).
The variant is “functionally related to glutamic acid metabolism, suggesting a mechanistic link,” the researchers wrote.
“Further studies are needed to dissect the mechanisms linking this locus to the development and progression of atherosclerosis in diabetes,” Qi and colleagues wrote. “As part of these efforts, it would be useful to extend the study to type 1 diabetes because this may provide clues about whether the gene x diabetes interaction involves hyperglycemia or instead concerns factors that are specific to type 2 diabetes, such as insulin resistance or some of the genes predisposing to this form of diabetes.”
Disclosure: See the full study for a list of the researchers’ relevant financial disclosures.
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