Scientists have identified a previously unknown genetic variant that is associated with an increased risk of coronary heart disease (CHD) in type 2 diabetic patients.
This discovery has the potential to lead to the development of new treatments for CHD in diabetic patients.
CHD is the leading cause of morbidity and mortality among diabetic patients. Diabetic individuals have a two- to threefold increased risk for CHD and two- to fourfold higher CHD morbidity and mortality rates.
Scientists in Genetics and Epidemiology at Joslin were interested in finding out whether there were genetic determinants of CHD specific to diabetic patients.
In collaboration with colleagues from the Harvard School of Public Health and research institutes in Italy, they conducted genome-wide association analyses of 1,517 type 2 diabetic patients with CHD and 2,671 type 2 diabetic subjects without CHD.
They compared the results to analyses of 737 non-diabetic participants with CHD and 1,637 non-diabetic participants without CHD.
The participants were selected from the Nurses Heath Study, Health Professionals Follow-up Study, Joslin Heart Study, Gargano Heart Study and Catanzaro Study.
A genetic variant in the region of the GLUL gene was identified that is associated with an increased risk of CHD in type 2 diabetics.
Alessandro Doria, M.D., Ph.D., M.P.H., co-senior author and an Investigator in the Section on Genetics and Epidemiology, Associate Professor of Medicine at Harvard Medical School, and Associate Professor in the Department of Epidemiology at the Harvard School of Public Health said that it is a common genetic variant that becomes important in the presence of diabetes. You need the presence of both diabetes and the variant to increase the risk of CHD.
Other senior author for the study Lu Qi, M.D., Ph.D., of the Harvard School of Public Health said that the findings may have particularly important implications regarding prevention and reduction of cardiovascular morbidity and mortality through dietary and lifestyle intervention in diabetic patients.
The genetic variant may affect CHD risk by reducing the expression of the GLUL gene which is involved in glutamine/glutamic acid metabolism. Research evidence indicates that glutamine/glutamic acid metabolism contributes to the regulation of insulin secretion and glucose metabolism. Several clinical trials suggest that glutamine may protect against cardiovascular disease. In addition, epidemiological studies have shown that abnormal metabolism of these amino acids is related to insulin resistance, type 2 diabetes and cardiovascular disorders. Further research is needed to better understand the relationship of glutamine/glutamic acid metabolism to the development of CHD.
Doria said that 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.
The findings have been published in the Journal of the American Medical Association (JAMA).
