CHD Risk in Diabetes Linked to a Gene

According to a new genome-wide association study (GWAS), a genetic variant has been associated with coronary heart disease among type 2 diabetic patients….

The study by Qi et al. included "5 independent sets of CHD cases and CHD-negative controls" from the Nurses’ Health Study (1976-2008), Health Professionals Follow-up Study (1986-2008), Joslin Heart Study (2001-2008), Gargano Heart Study (2001-2008), and Catanzaro Study (2004-2010). Among participants with type 2 diabetes, there were a total of 1,517 CHF cases and 2,671 controls. Individuals without diabetes consisted of 737 CHD cases and 1,637 CHD-negative controls. Results in diabetic patients were compared to those of non-diabetic patients. According to the authors, "exposures included 2,543,016 common genetic variants occurring throughout the genome."

Outcome measures of the study included incidence of coronary heart disease, coronary artery bypass grafting, percutaneous transluminal coronary angioplasty, or angiographic evidence of significant stenosis of the coronary arteries.

Among the many genetic factors diabetic participants were exposed to, the genetic variant on chromosome 1q25 (rs10911021) was consistently associated with an increased risk for CHD, whereas non-diabetic patients with CHD were shown to have no elevated risk due to this genetic variant. This is because in non-diabetic patients, risk allele frequencies were 0.697 in cases vs. 0.696 in controls (odds ratio, 0.99 [95% CI, 0.87-1.13]; P = .89). Furthermore, researchers found that homozygotes of this variant were associated with decreased expression of the glutamate ammonia ligase gene in human endothelial cells.

The authors concluded that the genetic variant rs10911021, caused by a single-nucleotide polymorphism is significantly associated with CHD risk among diabetic participants. In the future, this discovery may help researchers focus on specific drug targets or other interventions to decrease the risk of CHD in individuals with diabetes.

 Qi L et al. Association between a genetic variant related to glutamic acid metabolism and coronary heart disease in individuals with type 2 diabetes. JAMA. 2013 Aug 28;310(8):821-8. doi: 10.1001/jama