Association of Single Nucleotide Polymorphism in OCT1 and OCT3 Genes with the Efficacy of Metformin Response in North Indian Type 2 Diabetes Mellitus Patients.

Abstract

Abstract Purpose Interindividual variation in efficacy of metformin among type 2 diabetes mellitus (T2DM) patients have been associated with several genetic variants. Understanding the genetic pathways involved in pharmacodynamics of metformin can affect personalized treatment of T2DM. Our study aimed to find the implication of genetic polymorphism in organic cation transporters (OCT1 and OCT3) genes on drug efficacy of metformin therapy in T2DM patients from North India. Methods This study evaluated the role of OCT1 (rs628031) and OCT3 (rs2292334) polymorphism in metformin response on T2DM patients. Response to metformin was defined by HbA1c levels based on which patients (n = 177) were divided into two groups: responders (HbA1C < 7% ; n = 127) and non-responders (HbA1C ≥ 7%; n = 50). The responders were further subcategorized as T2DM patients on monotherapy (n = 55) and on combination therapy (n = 72). Genotyping was done using PCR-RFLP approach. Results No significant association was found between OCT1 (rs628031) polymorphism and metformin response in T2DM patients. On the other hand, significant association of OCT3 (rs rs2292334) polymorphism was observed with metformin response where AA genotype carriers showed higher efficacy of metformin both in mono [OR (CI) = 0.29(0.11–0.72) and p = 0.007] and combination therapy [OR (CI) = 0.41(0.16-1.0) and p = 0.047]. Also, A allele was more prevalent in responders [OR (CI) = 0.48(0.28–0.84) and p = 0.010] while G allele was found to be associated with inefficacy of metformin in T2DM patients [OR (CI) = 2.07(1.19–3.61) and p = 0.010]. Conclusion Genotyping of OCT3 (rs2292334) might be useful in predicting the response to metformin in T2DM patients.