Genetic Polymorphism of the OCT1 Gene (SLC22A1) and Association with the Development of Gastro-Intestinal Side Effects in Patients with Type 2 Diabetes mellitus on Metformin Therapy at the Baptist Hospital Etoug-Ebe, Yaounde- Cameroon

Author(s): Xaviera Jamieson Pouwawe Moumami, Calvino Fomboh Tah, Jean Paul Kengne Chedjou, Wilfried Olivier Ngandjeu Tchamdjeu, Lesley Ngum Ngum, Alice Catherine Ngo Ngue, Jenabu Yoru, Tatiana Tchakote Wami, Mjila Moise Mfouapon Mbowou, Mariam Tsamanga Ahmadou, Esdras Messoma Manyaka, Michelle Larissa Bakam Magoua, Michel Deukam, Akindeh Mbuh Nji, Wilfred Fon Mbacham

Diabetes mellitus is a metabolic disorder characterized by chronic hyperglycemia resulting from defects in insulin secretion, insulin action, or both. In order to manage diabetes, oral antihyperglycemic drugs are recommended among which, metformin, which is the first-line therapy for the treatment of Type 2 Diabetes mellitus (T2DM) worldwide. Evidence has demonstrated that 20–30% of patients treated with metformin could develop gastrointestinal (GI) side-effects, which could be attributed to genetic polymorphism in the gene (SLC22A1) coding for the protein responsible for metformin transport (Organic cation transporter 1). This study aimed at investigating the association between the OCT1 gene polymorphism M420del (rs72552763) and the development of gastro-intestinal side effects in T2DM patients on metformin therapy in Yaoundé, Cameroon. A case-control study was carried out on 210 participants from the Etoug-Ebe Baptist hospital from whom informed consent was gotten. DNA was extracted from dried blood spots (DBS) on Whartman N03 filter paper using the Chelex 100 method. Genotyping of the OCT1 gene (M420del) was done using the PCR-RFLP. The Chi squared test (X2) was used to establish associations and a p-value of <0.05 was considered statistically significant. The most predominant genotype was the homozygous mutant aa genotype (85.71%, 180/210) with respect to the heterozygous Aa genotype (14.29%, 30/210). No homozygous wild type (AA) observed amongst the study participants. Individuals possessing the aa genotype were 3 times more susceptible to development gastro-intestinal side effects (OR= 3.143, P=0.005). In conclusion, an association was found between the OCT1 gene polymorphism M420del and the development of GI side effects.