Association between the synonymous variant organic cation transporter 3 (OCT3)-1233G>A and the glycemic response following metformin therapy in patients with type 2 diabetes

Objective(s): Organic cation transporter 3 (OCT3) as a high-capacity transporter contribute to the metabolism of metformin. The present study was conducted to determine the genotype frequencies of the variant OCT3-1233G>A (rs2292334) in patients with newly diagnosed type 2 diabetes (T2D) and its relationship with response to metformin. Materials and Methods: This study included 150 patients with T2D who were classified into two groups following three months of metformin therapy: responders (by more than 1% reduction in HbA1c from baseline) and nonresponders (less than 1% reduction in HbA1c from baseline). PCR-based restriction fragment length polymorphism (RFLP) served to genotype OCT3-564G>A variant. Results: The parameters such as HbA1c (P<0.001) and BMI (P<0.001) in both patients with GA + AA genotype and GG genotype decreased significantly following 3 months of metformin therapy compared with baseline. The mean reduction in HbA1c levels following 3 months was higher in patients with the A allele (0.77% reduction from baseline) than in those with the homozygous G allele (0.54% reduction from baseline). Also, in GA + AA genotypes compared with GG genotypes, the mean reduction in HbA1c values from baseline was 0.34% for responders and 0.14% for non-responders. Conclusion: Considering the roles of genetic variations in the function of metformin transporters, the effect of variations such as 1233G>A in the OCT3, which is a high-capacity transporter widely expressed in various tissues cannot be ignored. Comparing the allele frequencies of OCT3-1233G>A variant in our study and different ethnic populations confirm that the variant is a highly polymorphic variant.