Association between the synonymous variant organic cation transporter ۳ (OCT۳)-۱۲۳۳G>A and the glycemic response following metformin therapy in patients with type ۲ diabetes

Objective(s): Organic cation transporter ۳ (OCT۳) as a high-capacity transporter contribute to the metabolism of metformin. The present study was conducted to determine the genotype frequencies of the variant OCT۳-۱۲۳۳G>A (rs۲۲۹۲۳۳۴) in patients with newly diagnosed type ۲ diabetes (T۲D) and its relationship with response to metformin. Materials and Methods: This study included ۱۵۰ patients with T۲D who were classified into two groups following three months of metformin therapy: responders (by more than ۱% reduction in HbA۱c from baseline) and nonresponders (less than ۱% reduction in HbA۱c from baseline). PCR-based restriction fragment length polymorphism (RFLP) served to genotype OCT۳-۵۶۴G>A variant. Results: The parameters such as HbA۱c (P<۰.۰۰۱) and BMI (P<۰.۰۰۱) in both patients with GA + AA genotype and GG genotype decreased significantly following ۳ months of metformin therapy compared with baseline. The mean reduction in HbA۱c levels following ۳ months was higher in patients with the A allele (۰.۷۷% reduction from baseline) than in those with the homozygous G allele (۰.۵۴% reduction from baseline). Also, in GA + AA genotypes compared with GG genotypes, the mean reduction in HbA۱c values from baseline was ۰.۳۴% for responders and ۰.۱۴% for non-responders. Conclusion: Considering the roles of genetic variations in the function of metformin transporters, the effect of variations such as ۱۲۳۳G>A in the OCT۳, which is a high-capacity transporter widely expressed in various tissues cannot be ignored. Comparing the allele frequencies of OCT۳-۱۲۳۳G>A variant in our study and different ethnic populations confirm that the variant is a highly polymorphic variant.

Keywords:

HbA۱c , Metformin , OCT۳ , Organic cation transporter ۳ , Type ۲ diabetes