Genetic variant may connect dots between heart disease & diabetes

Researchers identified a genetic variant that may be the smoking gun in coronary heart disease (CHD) risk in people with type 2 diabetes. The genetic variant was associated with a 36 percent increased risk of CHD in diabetic people but not in nondiabetics.

Lu Qi, MD, PhD, of Brigham and Women’s Hospital in Boston, and colleagues reported in the Aug. 28 issue of JAMA that they identified a single-nucleotide polymorphism that appeared to affect CHD risk in diabetic people. The genetic variant plays a role in the metabolism of glutamic acid, which is involved in the regulation of insulin secretion.

Qi and colleagues based their three-stage genome-wide analysis study on data from the Nurses’ Health Study, Health Professionals Follow-up Study, the Joslin Heart Study and the Gargano Heart Study. The primary outcome was CHD, which they defined as nonfatal MI, CABG, PCI or significant stenosis of the coronary arteries detected by angiography.

The analysis included 1,517 people with type 2 diabetes and CHD; 2,671 people with diabetes but no CHD; 737 nondiabetic people with CHD and 1,637 nondiabetic people without CHD. They compared results from diabetic participants with results from nondiabetic particpants with and without CHD.

All in all, they tested more than 2.5 million genetic variants for an association with CHD to home in on a variant in the region of the GLUL gene. In nondiabetic participants, the genetic variant appeared to either be very weakly associated with CHD or not associated.  But it was associated with a 36 percent increased risk of CHD in people with type 2 diabetes.

“The locus is in the region of the GLUL gene on chromosome 1q25 and may affect CHD risk by reducing the expression of this gene and affecting glutamate and glutamine metabolism in endothelial cells,” they wrote. “This genetic variant appeared to be specifically associated with CHD in the diabetic population and showed a significant gene-by-diabetes synergism on CHD risk.”

They recommended more studies to examine the biological mechanisms that might tie the genetic variant to disease risk.

In press releases, the researchers added that the finding may help to develop treatments and interventions for CHD in people with type 2 diabetes. “This finding may have particularly important implications regarding prevention and reduction of cardiovascular morbidity and mortality through dietary and lifestyle intervention in diabetic patients,” Qi said.