Gene Variation, Poor Glycemic Control Increase Heart Risk

Certain genetic variations can increase the risk of developing coronary artery disease in the general population. For people with type 2 diabetes with that same genetic variation, their risk increases significantly with poor glycemic control.

Patients with type 2 diabetes who have poor glycemic control and a certain genetic variation have an increased risk of coronary artery disease, according to a study in the November 26 issue of JAMA.

Among the known risk factors for cardiovascular disease, diabetes mellitus ranks as one of the most potent. It increases the lifetime risk of a major cardiac event by 2 to 4 times, relative to individuals without diabetes, according to background information in the article. A substantial proportion of cardiovascular risk is under the control of genetic factors.

Genetic variation on chromosome 9p21 has been associated with increased risk of coronary artery disease (CAD) in the general population. Alessandro Doria, M.D., Ph.D., M.P.H., of the Joslin Diabetes Center, Harvard Medical School, Boston, and colleagues examined the association of this genetic variant with coronary artery disease in individuals with type 2 diabetes and whether the association is affected by poor glycemic control.

The researchers conducted two studies, with one including 734 type 2 diabetes patients (322 with angiographically diagnosed CAD and 412 with no evidence of CAD), who were recruited between 2001 and 2006; the other study included 475 type 2 diabetes patients whose survival status was monitored from their recruitment between 1993 and 1996 until December 31, 2004.

Participants for both studies were tested for a gene variation of chromosome 9p21 as well as their glycemic control by averaging measurements of hemoglobin A1c (HbA1c) taken in the years before study entry.

Researchers found that patients with the gene variation, but good glycemic control had double the risk of CAD. Patients with both the gene variation and poor glycemic control had four times the risk of developing coronary artery disease.

A similar interaction between the 9p21 variant and poor glycemic control was observed with respect to the rate of death after 10 years.

"In conclusion, 9p21 [variant] and poor glycemic control interact in determining the odds of CAD in type 2 diabetes,” the authors write. “This finding may have implications for our understanding of atherogenesis [the process of plaque forming in arteries] in diabetes and for the design of more effective prevention strategies."