HealthDay News — A variant of a gene associated with glutamic acid metabolism increases heart disease risk in patients with diabetes, results of a genome-wide association study indicate.

The single-nucleotide polymorphism (SNP), rs10911021, on chromosome 1q25 was associated with a 36% increased odds of coronary heart disease among patients with diabetes (P=2×10-8), Lu Qi, MD, PhD, from the Harvard School of Public Health in Boston, and colleagues reported in the Journal of the American Medical Association.

However, the SNP was not linked to heart disease risk among patients without diabetes (P=0.89), the researchers found. Previous studies have shown that glutamic acid helps regulate insulin secretion and glucose metabolism.

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For the current study, Qi and colleagues analyzed data from a cohort of 1,517 patients with coronary heart disease and 2,671 controls without the disease, all of whom had diabetes who participated in the Nurses’ Health Study, Health Professionals Follow-up Study, Joslin Heart Study, Gargano Heart Study and Catanzaro Study.

Another 737 coronary heart disease cases without diabetes and 1,637 without either disease were also included for comparison from the Nurses’ Health Study and Health Professionals Follow-up Study.

The researchers found a significant association between variant rs10911021 present on chromosome 1q25 and the risk of coronary heart disease in patients with diabetes (risk allele frequency, 0.733 vs 0.679; odds ratio 1.36, 95% CI:1.22-1.51). There was no association with this variant in patients without diabetes.

Risk allele homozygotes had a significant 32% decrease in expression of the glutamate-ammonia ligase gene and a significantly reduced ratio of pyroglutamic and glutamic acid. The metabolism of glutamine and glutamic acid has been shown to contribute to the regulation of insulin secretion and glucose metabolism, according to the researchers.

“A single-nucleotide polymorphism (rs10911021) was identified that was significantly associated with coronary heart disease among persons with diabetes but not in those without diabetes and was functionally related to glutamic acid metabolism, suggesting a mechanistic link,” the researchers concluded.

They called for further studies to better understand the biological mechanisms underlying the association.


  1. Qi L et al. JAMA 2013; 310: 821-828.