Several studies suggest that some triglyceride (TG)-associated single nucleotide polymorphisms (SNPs) have pleiotropic and opposite effects on glycemic traits. This potentially implicates them in pathways such as de novo lipogenesis, which is presumably up-regulated in the context of insulin resistance.
[Photo: Dr. Yann Klimentidis]
Dr. Yann Klimentidis, an assistant professor who studies genetic epidemiology at the University of Arizona Mel and Enid Zuckerman College of Public Health and a colleague tested whether the association of TG-associated SNPs with TG levels differs according to one’s level of insulin resistance. The study was published in the journal Circulation: Cardiovascular Genetics.
In three cohort studies looking at 12,487 people, the researchers tested the interaction of established TG-associated SNPs (individually and collectively) with several traits related to insulin resistance, on TG levels. They also tested the interaction of TG SNPs with fasting insulin (FI)-associated SNPs, individually and collectively, on TG levels. They found that the association of the TG genetic risk score with TG was over 60 percentstronger among those in the highest tertile of insulin resistance, compared to those in the lowest tertile. Individual SNPs contributing to this trend included those in/near GCKR, CILP2, and IRS1, while PIGV-NROB2 and LRPAP1 displayed an opposite trend of interaction. In the pooled dataset, they also identified a significant SNP-by-SNP interaction involving a TG-associated SNP near MIR148A, with a FI-associated in ARL15.
Dr. Klimentidis said the findings may provide genetic evidence for the upregulation of TG levels in insulin resistant individuals, in addition to identifying specific genetic loci and a SNP-by-SNP interaction implicated in this process.
Interaction of insulin resistance and related genetic variants with triglyceride-associated genetic variants.
Circulation: Cardiovascular Genetics. February 2016