The effect of the Organic Cation Transporters! (OCT1) gene polymorphism on the therapeutic efficacy of metformin in type 2 diabetic patients in Basrah/ Southern Iraq
Keywords:
Type 2 diabetes mellitus, Metformin, SNP, rs12208357/R61C, rs72552763/Met420delAbstract
Metformin does not undergo metabolism inside the body and is excreted in the urine unchanged. The organic cation transporter1 (OCT1) is one of the most numerous hepatic transporters and has an essential function in the hepatic transport of metformin. The study objectives are to research the prevalence of two (single nucleotide polymorphism) SNP [rs12208357] and [rs72552763] of (OCT1) of SLC22A1 gene in type 2 diabetes mellitus (T2DM) patients in (Basrah city)/South of Iraq and to investigate the association between these SNPs and metformin efficacy. It is a prospective cohort study. The study involved one hundred and two adult patients recruited from two large tertiary care centers in Basrah city. All the patients received immediate-release metformin tablets 1g twice daily for three months. Laboratory data included (HbA1C) and fasting blood glucose (FBG) initially and later after three months of the study. Metformin responders are patients whose HbA1c values are reduced by ≥1% after 90 days of metformin monotherapy. All enrolled patients were genotyped for two of the most prevalent SNPs in the OCT1 gene by using ARMS- PCR genotyping assays. Inclusion criteria include: newly diagnosed (drug naïve) T2DM patients with HbA1C range (6.5-9.9), ages ranging from 25 and 75 years old, and signed consent from all the participants. This study had 33 non-responders, and the reduction in FBG and HbA1C levels in the responder's group was significant (p-value ˂ 0.05) after 90 days of treatment. The patients with homozygous genotype (CC) of rs12208357 and (AA) of rs72552763 gene polymorphism were characterized by good therapeutic efficacy of metformin.
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