A Metformin Pharmacogenetic Study of Patients with Type 2 Diabetes Mellitus and SLC22A1 Gene Mutation


  • Elly Usman Department of Pharmacology, Faculty of Medicine, Universitas Andalas, Padang, Indonesia
  • Yusticia Katar Department of Pharmacology, Faculty of Medicine, Universitas Andalas, Padang, Indonesia




Fasting blood glucose, Metformin, SLC22A1, T2DM, Pharmacogenetic


Background: The purpose of this study was to determine the profiles of patients with type 2 diabetes (T2DM) and an SLC22A1 gene mutation in order to evaluate the effect of metformin pharmacogenetics.

Methods: To assess the effect of pharmacogenetics, a mutation of the SLC22A1 gene in T2DM patients receiving metformin was investigated. Blood samples were taken from 50 diabetics of Minangkabau ethnicity who met the inclusion criteria, and SNP genotyping and blood glucose levels were determined. DNA is extracted and purified from blood samples using DNAzol® Genomic DNA Kits (Thermofischer Scientific) reagents. The Chi-square test and Independent sample T test were used to analyze the data. A statistically significant association was defined as a p-value < 0.05. Finally, the GraphPad Prism 7.00 program was used to gather and analyze data.

Results: The adjusted odds ratio for inadequate fasting blood glucose was 1.48 (95% CI 1.18-1.95) in this study, while the adjusted odds ratio for diet discipline was 1.23 (95% CI 1.18-1.95). The adjusted odds ratio for low physical activity was 1.18. (95% CI 1.05-1.81). According to the sequencing data, the proportion of mutants is high at exon 2 rs683369 (G> C), while the percentage of wildtype and heterozygous mutants is the same at introns rs4646272 (T> G).

Conclusion: Obesity, diet discipline, and low physical activity were all found to increase the likelihood of insufficient fasting blood glucose in T2DM patients. Exon 2 rs683369 (G> C) has a high proportion of mutants, but introns rs4646272 (T> G) have the same percentage of wildtype and heterozygous mutants.


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Arimany-Nardi C, Koepsell H, Pastor-Anglada M. Role of SLC22A1 polymorphic variants in drug disposition, therapeutic responses, and drug-drug interactions. Pharmacogenomics J. 2015;15(6):473-87. https://doi.org/10.1038/tpj.2015.78 PMid:26526073 DOI: https://doi.org/10.1038/tpj.2015.78

Boney CM, Verma A, Tucker R, Vohr BR. Metabolic syndrome in childhood: Association with birth weight, maternal obesity, and gestational diabetes mellitus. Pediatrics. 2005;115(3):e290-6. https://doi.org/10.1542/peds.2004-1808 PMid:15741354 DOI: https://doi.org/10.1542/peds.2004-1808

Ministry of Health Republic of Indonesia. Basic Health Research. Ministry of Health Republic of Indonesia. Jakarta: Ministry of Health Republic of Indonesia; 2013.

Levitan EB, Song Y, Ford ES, Liu S. Is nondiabetic hyperglycemia a risk factor for cardiovascular disease?: A meta-analysis of prospective studies. Arch Intern Med. 2004;164(19):2147-55. https://doi.org/10.1001/archinte.164.19.2147 PMid:15505129 DOI: https://doi.org/10.1001/archinte.164.19.2147

Shu Y, Brown C, Castro R, Shi R, Lin E, Owen R, et al. Effect of genetic variation in the organic cation transporter 1, OCT1, on metformin pharmacokinetics. Clin Pharmacol Ther. 2008;83(2):273-80. https://doi.org/10.1038/sj.clpt.6100275 PMid:17609683 DOI: https://doi.org/10.1038/sj.clpt.6100275

Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferrannini E, Nauck M, et al. Management of hyperglycemia in Type 2 diabetes: A patient-centered approach position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care. 2012;35(6):1364-79. https://doi.org/10.2337/dc12-0413 PMid:22517736 DOI: https://doi.org/10.2337/dc12-1184

Kahn SE, Cooper ME, Del Prato S. Pathophysiology and treatment of Type 2 diabetes: Perspectives on the past, present, and future. Lancet. 2014;383(9922):1068-83. https://doi.org/10.1016/S0140-6736(13)62154-6 PMid:24315620 DOI: https://doi.org/10.1016/S0140-6736(13)62154-6

DeFronzo RA, Goodman AM. Efficacy of metformin in patients with non-insulin-dependent diabetes mellitus. N Engl J Med. 1995;333(9):541-9. https://doi.org/10.1056/NEJM199508313330902 PMid:7623902 DOI: https://doi.org/10.1056/NEJM199508313330902

Becker ML, Visser LE, van Schaik RH, Hofman A, Uitterlinden AG, Stricker BHC. Genetic variation in the organic cation transporter 1 is associated with metformin response in patients with diabetes mellitus. Pharmacogenom J. 2009;9:242-7. https://doi.org/10.1038/tpj.2009.15 PMid:19381165 DOI: https://doi.org/10.1038/tpj.2009.15

Ajlouni K, Khader YS, Batieha A, Ajlouni H, El-Khateeb M. An increase in prevalence of diabetes mellitus in Jordan over 10 years. J. Diabetes Complicat. 2008;22(5):317-24. https://doi.org/10.1016/j.jdiacomp.2007.01.004 PMid:18413210 DOI: https://doi.org/10.1016/j.jdiacomp.2007.01.004

Song I, Shin H, Shim E, Jung I, Kim W, Shon J, Shin J. Genetic variants of the organic cation transporter 2 influence the disposition of metformin. Clin Pharmacol Ther. 2008;84:559-62. DOI: https://doi.org/10.1038/clpt.2008.61

Wang ZJ, Yin OQ, Tomlinson B, Chow MS. OCT2 polymorphisms and in-vivo renal functional consequence: Studies with metformin and cimetidine. Pharmacogenet Genom. 2008;18(7):637-45. https://doi.org/10.1097/FPC.0b013e328302cd41 PMid:18551044 DOI: https://doi.org/10.1097/FPC.0b013e328302cd41

Tzvetkov MV, Vormfelde SV, Balen D, Meineke I, Schmidt T, Sehrt D, et al. The effects of genetic polymorphisms in the organic cation transporters OCT1, OCT2, and OCT3 on the renal clearance of metformin. Clin Pharmacol Ther. 2009;86(3):299-306. https://doi.org/10.1038/clpt.2009.92 PMid:19536068 DOI: https://doi.org/10.1038/clpt.2009.92

Mahrooz A, Alizadeh A, Hashemi-Soteh MB, Ghaffari-Cherati M, Hosseyni-Talei SR. The polymorphic variants rs3088442 and rs2292334 in the organic cation transporter 3 (OCT3) gene and susceptibility against Type 2 diabetes: Role of their interaction. Arch Med Res. 2017;48(2):162-8. https://doi.org/10.1016/j.arcmed.2017.03.010 PMid:28625319 DOI: https://doi.org/10.1016/j.arcmed.2017.03.010

Tuomi T, Santoro N, Caprio S, Cai M, Weng J. Groop, L. The many faces of diabetes: A disease with increasing heterogeneity. Lancet. 2014;383(9922):1084-94. https://doi.org/10.1016/S0140-6736(13)62219-9 PMid:24315621 DOI: https://doi.org/10.1016/S0140-6736(13)62219-9

Karalliedde J, Gnudi L. Diabetes mellitus, a complex and heterogeneous disease, and the role of insulin resistance as a determinant of diabetic kidney disease. Nephrol Dial Transplant. 2014;31(2):gfu405. https://doi.org/10.1093/ndt/gfu405 PMid:25550448 DOI: https://doi.org/10.1093/ndt/gfu405

Lango H, Palmer CN, Morris AD, Zeggini E, Hattersley AT, McCarthy MI, et al. Assessing the combined impact of 18 common genetic variants of modest effect sizes on Type 2 diabetes risk. Diabetes. 2008;57(11):3129-35. https://doi.org/10.2337/db08-0504 PMid:18591388 DOI: https://doi.org/10.2337/db08-0504

Nigam SK. The SLC22 transporter family: A Paradigm for the impact of drug transporters on metabolic pathways, signaling, and disease. Annu Rev Pharmacol Toxicol. 2018;58:663-87. https://doi.org/10.1146/annurev-pharmtox-010617-052713 PMid:29309257 DOI: https://doi.org/10.1146/annurev-pharmtox-010617-052713

Pochini L, Galluccio M, Scalise M, Console L, Indiveri C. OCTN: A small transporter subfamily with great relevance to human pathophysiology, drug discovery, and diagnostics. SLAS Discov. 2019;24(2):89-110. https://doi.org/10.1177/2472555218812821 PMid:30523710 DOI: https://doi.org/10.1177/2472555218812821

Dujic T, Zhou K, Yee S, van Leeuwen N, de Keyser C, Javorský M, et al. Variants in pharmacokinetic transporters and glycemic response to metformin: A metgen meta-analysis. Clin Pharmacol Ther. 2017;101(6):763-72. https://doi.org/10.1002/cpt.567 PMid:27859023 DOI: https://doi.org/10.1002/cpt.567

Al-Eitan LN, Amomani BA, Nassar AM, Elsaqa BZ, Saadeh NA. Metformin pharmacogenetics: Effects of SLC22A1, SLC22A2, and SLC22A3 polymorphisms on glycemic control and HbA1c levels. J Pers Med. 2019;9(1):17. https://doi.org/10.3390/jpm9010017 PMid:30934600 DOI: https://doi.org/10.3390/jpm9010017

Wondmkun YT. Obesity, insulin resistance, and Type 2 diabetes: Associations and therapeutic implications. Diabetes Metab Syndr Obes. 2020;13:3611-6. https://doi.org/10.2147/DMSO.S275898 PMid:33116712 DOI: https://doi.org/10.2147/DMSO.S275898

Sami W, Ansari T, Butt NS, Hamid MR. Effect of diet on Type 2 diabetes mellitus: A review. Int J Health Sci (Qassim). 2017;11(2):65-71. PMid:28539866

Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, et al. Exercise and Type 2 diabetes: The American college of sports medicine and the American diabetes association: Joint position statement. Diabetes Care. 2010;33(12):e147-67. https://doi.org/10.2337/dc10-9990 PMid:21115758 DOI: https://doi.org/10.2337/dc10-9990




How to Cite

Usman E, Katar Y. A Metformin Pharmacogenetic Study of Patients with Type 2 Diabetes Mellitus and SLC22A1 Gene Mutation. Open Access Maced J Med Sci [Internet]. 2022 Feb. 16 [cited 2024 Mar. 5];10(A):273-7. Available from: https://oamjms.eu/index.php/mjms/article/view/8473