Diabetes, Metabolic Syndrome and Obesity (Aug 2023)
Association of Met420del Variant of Metformin Transporter Gene SLC22A1 with Metformin Treatment Response in Ethiopian Patients with Type 2 Diabetes
Abstract
Abraham Degaga,1,2 Sisay Sirgu,3 Hasniza Zaman Huri,2 Maw Shin Sim,4 Tedla Kebede,5 Birhanemeskel Tegene,6 Navin Kumar Loganadan,7 Ephrem Engidawork,1 Workineh Shibeshi1 1Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia; 2Department of Clinical Pharmacy & Pharmacy Practice, Faculty of Pharmacy, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Internal Medicine, Diabetes and Endocrinology Unit, Saint Paul Hospital Millennium Medical College, Addis Ababa, Ethiopia; 4Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, University of Malaya, Kuala Lumpur, Malaysia; 5Department of Internal Medicine, Diabetes and Endocrinology Unit, Addis Ababa University, Addis Ababa, Ethiopia; 6Department of Microbiology, Saint Paul Hospital Millennium Medical College, Addis Ababa, Ethiopia; 7Department of Pharmacy, Putrajaya Hospital, Precinct 7, Putrajaya, 62250, MalaysiaCorrespondence: Workineh Shibeshi, Department of Pharmacology and Clinical Pharmacy, School of Pharmacy, College of Health Sciences, Addis Ababa University, P.O.Box 9086, Addis Ababa, Ethiopia, Tel +251 927361143, Email [email protected]: This study aimed to evaluate whether the M420del variants of SLC22A1 (rs72552763) is associated with metformin treatment response in Ethiopian patients with type 2 diabetes mellitus (T2DM).Patients and Methods: A prospective observational cohort study was conducted on 86 patients with T2DM who had been receiving metformin monotherapy for < 1 year. Patients showing ≥ 0.5% reduction in HbA1c levels from baseline within 3 months and remained low for at least another 3 months were defined as responders while those patients with < 0.5% reduction in HbA1c levels and/or those whom started a new class of glucose-lowering drug(s) because of unsatisfactory reduction were defined as non-responders. In addition, good glycemic control was observed when HbA1c ≤ 7.0%, and the above values were regarded as poor. Genotyping of rs72552763 SNP was performed using TaqMan® Drug Metabolism Enzyme Genotyping Assay and its association with metformin response and glycemic control were assessed by measuring the change in HbA1c and fasting blood glucose levels using Chi-square, logistic regression and Mann–Whitney U-test. Statistical significance was set at p < 0.05.Results: The minor allele frequency of the rs72552763 SNP of SLC22A1 was 9.3%. Metformin response was significantly higher in deletion_GAT (del_G) genotypes as compared to the wild-type GAT_GAT (G_G) genotypes. Furthermore, a significantly lower median treatment HbA1 level was found in del_G genotypes as compared to G_G genotypes. However, the association of rs72552763 with metformin response was not replicated at the allele level. In contrast, the minor del_allele was significantly associated with good glycemic control compared to the G_allele, though not replicated at del_G genotypes level.Conclusion: This study demonstrated that metformin response was significantly higher in study participants with a heterozygous carrier of M420del variants of SLC22A1 as compared to the wild-type G_G genotypes after 3 months of treatment.Keywords: T2DM, glycemic response, metformin, SLC22A1 gene, Met420del, Ethiopia
