Intronic Variants in OCT1 are Associated with All-Cause and Cardiovascular Mortality in Metformin Users with Type 2 Diabetes.

ABSTRACT: Purpose:Organic cation transporters (Octs) use cations like endogenous compounds, toxins, and drugs, such as metformin, as substrates. Therefore, these proteins determine the pharmacokinetics and -dynamics of metformin and thus its efficacy. Of note, metformin is today the most commonly used pharmaceutical in the treatment of type 2 diabetes (T2DM) with nevertheless a great variability in clinical response, which attributes to genetic variances. The aim of this study was to determine the influence of intronic OCT1 SNPs on prevalence of all-cause and cardiovascular death. Patients and Methods:Genotypes of 27 intronic SNPs in OCT1 were investigated in the LURIC study, a prospective cohort of 3316 participants scheduled for coronary angiography. We investigated whether these variants were associated with all-cause and cardiovascular death in 73 individuals with T2DM under metformin therapy, in individuals without diabetes, individuals with T2DM and individuals with T2DM without metformin therapy. Results:In a multivariate Cox regression analysis adjusted for classical cardiovascular risk factors, 4 intronic OCT1 SNPs were significantly associated with all-cause and cardiovascular mortality in individuals with T2DM on metformin therapy. Conclusion:According to their OCT1 genotype, some individuals with T2DM on metformin therapy might be prone to an increased risk of cardiovascular death.

SUBMITTER: Schweighofer N 

PROVIDER: S-EPMC7308180 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature