August 28, 2013
Genetic Variant Leads To Increased Risk Of Cardiac Heart Disease In Type 2 Diabetics
Lee Rannals for redOrbit.com - Your Universe Online
Scientists have identified a previously unknown genetic variant associated with coronary heart disease (CHD) in type 2 diabetic patients. This discovery, published in JAMA, could eventually lead to the development of new treatments for CHD in diabetic patients.
More than 370 million people around the globe have type 2 diabetes, and CHD is the leading cause of death among diabetic patients. Type 2 diabetic patients have a two- to three-fold risk in developing CHD.
Researchers conducted genome-wide association analyses of 1,517 type 2 diabetic patients with CHD and 2,671 type 2 diabetic patients without the heart disease. They compared the results to analyses of 737 non-diabetic patients who had CHD and 1,637 non-diabetic participants without CHD. They identified a genetic variant in the region of the GLUL gene that is associated with an increased risk of CHD in 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," Lu Qi, senior author for the study, from Harvard School of Public Health in Boston, said in a statement.
The genetic variant may affect CHD risk by reducing the expression of the GLUL gene which is involved in glutamine/glutamic acid metabolism. This gene encodes a key enzyme regulating the conversion of glutamic acid to glutamine. It was consistently associated with a 36 percent increased risk in CHD in people with diabetes.
Research indicates that glutamine/glutamic acid metabolism contributes to the regulation of insulin secretion and glucose metabolism.
"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," the authors 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."
Several clinical trials show that glutamine may protect against cardiovascular disease. However, further research could help scientists better understand the relationship between glutamine/glutamic acid metabolism and the development of CHD. The authors said further studies need to be done in order to fully understand the biological mechanisms linking the gene variant to CHD in diabetic patients.
"The identification of this genetic variant opens up the possibility of developing treatments that are specifically aimed at breaking the links between diabetes and CHD," said Alessandro Doria, co-senior author and an Investigator in the Section on Genetics and Epidemiology at Joslin Diabetes Center. "It may give us new insights into the mechanisms underlying the increased risk of CHD in diabetic individuals and enable us to identify targets for new cardioprotective drugs that are specific for the diabetic population."