Genetic Polymorphism in the Organic Cation Transporters 1 (OCT1) Gene and its Effect on Therapeutic Efficacy and Gastrointestinal Side Effects of Metformin in Patients with Type 2 Diabetes Mellitus in Basrah/ Southern Iraq.

Abstract

Objectives: This study aims to detect the association of the OCT1 genetic polymorphism with the efficacy and gastrointestinal side effects of metformin in newly diagnosed type 2 diabetes and drug naïve patients in Basrah/Southern Iraq. Methods: This was a prospective cohort population-based study of (102) newly diagnosed type 2 diabetics from February 2022 to December 2022. Newly diagnosed type 2 diabetes, drug naïve patients with an HbA1c range of (6.5-9.9) were included in the study. All the participants received immediate-release metformin. Metformin responders were patients whose HbA1c levels decreased by ≥1% after three months of treatment. Patients were genotyped for one of the most common SNPs in the OCT1 gene (SLC22A1): M420del (rs72552763) of axon 7, using ARMS- PCR genotyping assays. Results: Gastrointestinal side effects were observed in 15% of the patients. Out of the total of 102 participants, 69 were responders and 33 were non-responders. The homozygous genotype (AA) “reference type” of the SLC22A1 (rs72552763) gene polymorphism was significantly found in the responders' group; p-value = 0.0001. The homozygous genotypes (deletion/deletion) of the SLC22A1 (rs72552763) gene were more common among the non-responders' group; p-value = 0.0001. About 87% of those with gastrointestinal side effects carried the AA genotype. All the patients without gastrointestinal side effects carried the homozygous del/del genotype; P-value 0.005. Conclusions There was a significant association between the rs72552763 gene polymorphism and metformin efficacy and GI side effects.