Scientists from the Harvard School of Public Health have identified a single-nucleotide polymorphism that was significantly associated with coronary heart disease (CHD) among persons with diabetes but not in those without the disorder. The SNP, rs10911021, was functionally related to glutamic acid metabolism.
Lu Qi, M.D., Ph.D., of the Harvard School of Public Health, Boston, and colleagues conducted a study to identify genetic determinants of CHD that are specific to patients with diabetes.
The researchers studied a total of 1,517 CHD cases and 2,671 CHD-negative controls, all with type 2 diabetes. Results in patients with diabetes were compared with those in 737 nondiabetic CHD cases and 1,637 nondiabetic CHD-negative controls.
Of the 2,543,016 genetic variants that were tested for association with CHD in stage 1 of the 3-stage genome-wide analysis, 26 met the criterion for promotion to stage 2, and 3 of these further met the criterion for promotion to stage 3. Of the 3 variants that were promoted to stage 3, a SNP on chromosome 1q25 was consistently associated with CHD risk among diabetic participants. No association between this variant and CHD was detected among nondiabetic participants.
“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,” explained Dr. Qi. “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.”
The team plans to carry out further studies on the biological mechanisms linking the SNP to CHD in diabetes.
“As part of these efforts, it would be useful to extend the study to type 1 diabetes because this may provide clues about whether the gene x diabetes interaction involves hyperglycemia or instead concerns factors that are specific to type 2 diabetes, such as insulin resistance or some of the genes predisposing to this form of diabetes,” wrote the scientists in their paper. “However, the lack of interaction in our study between rs10911021 and genetic variants predisposing to type 2 diabetes make the latter hypothesis unlikely.”
The study, “Association Between a Genetic Variant Related to Glutamic Acid Metabolism and Coronary Heart Disease in Individuals With Type 2 Diabetes”, was published today in JAMA.