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

Overview

Journal Diabetes Metab Syndr Obes

Publisher Dove Medical Press

Specialty Endocrinology

Date 2020 Jul 2

PMID 32606866

Citations 1

Authors

Natascha Schweighofer

Bernd Genser

Winfried Maerz

Marcus E Kleber

Olivia Trummer

Thomas R Pieber

Barbara Obermayer-Pietsch

Affiliations

Soon will be listed here.

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.

Citing Articles

Exome Sequence Data of Eight SLC Transporters Reveal That and Variants Alter Metformin Pharmacokinetics and Glycemic Control.

Morales-Rivera M, Alemon-Medina R, Martinez-Hernandez A, Contreras-Cubas C, Altamirano-Bustamante N, Gomez-Garduno J Pharmaceuticals (Basel). 2024; 17(10).

PMID: 39459024 PMC: 11510168. DOI: 10.3390/ph17101385.

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