Highlights From the Latest in Diabetes Research

Enhanced CHD Risk in Diabetes: New Insight Into the Genetics of Glutamic Acid Metabolism

Although it has been known for some time that genetic factors can act to enhance the risk for coronary heart disease (CHD), it has been less clear why these factors often show a differential impact among diabetic and nondiabetic individuals. As the prevalence of diabetes continues to increase worldwide, improved understanding of the mechanisms underpinning the impact of specific genes on CHD risk in diabetes might offer new opportunities for interventions that target specific mechanisms of glucose metabolism among high-risk diabetic individuals. A new report by Qi et al. used data from five large cohort studies and showed that rs10911021, a variant on chromosome 1q25 that is functionally related to glutamic acid metabolism, may be a genetic factor that acts to enhance CHD risk in the presence of diabetes, but not when diabetes is absent. The report used a three-stage approach to examine the impact of this variant on the odds of CHD among diabetic case subjects and control subjects across the cohorts. Among diabetic individuals, there was a significant association between rs10911021 and odds of CHD (odds ratio [OR] = 1.36, 95% CI 1.22–1.51) but this association was absent among nondiabetic individuals from the same studies (OR = 0.99, 95% CI 0.87–1.13). The differential impact of the variant suggests that it interacts with diabetes to enhance CHD risk. Further investigation of protective and risk-enhancing alleles in human endothelial cells showed a nearly one-third reduction in the expression of the glutamate-ammonia ligase (GLUL) gene, as well as a lower ratio of pyroglutamic and glutamic acid. When the decreased ratio …

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  1. doi: 10.2337/db13-dd12 Diabetes vol. 62 no. 12 4286-4287
  1. Free via Open Access: OA