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Abstract Individual variability in drug efficacy and drug safety is a major challenge in current clinical practice, drug development, and drug regulation. Studies of pharmacogenetics have provided ample examples of causal relations between genotypes and drug response to account for phenotypic variations of clinical importance in drug therapy. Overcoming the obstacles holds promise for achieving the ultimate goal of effective and safe medication to targeted patients with appropriate genotypes[Qiang and Anthony,2011]. Metformin, an oral glucose-lowering drug, is widely used to treat type 2 diabetes and to delay or prevent its onset in people at high risk of the disease [Diabetes Care., 2011]. Metformin is actively transported into the liver, where it exerts its primary action, and then is actively transported from the liver into bile and blood stream. Elimination from the liver is mediated in part by the multidrug and toxin extrusion protein (MATE1), a membrane-bound transporter protein [Ostuka et al., 2005]. Aim of work: 1- Analyze the frequency of MATE gene among the Metformin non responder Egyptian Diabetic patients. 2-demonstrate the role of rs2289669 polymorphism on Metformin response. Patients and Methods: This study included 44 newly diagnosed type 2 diabetic patients (Sample size was calculated using whom HbA1c is between 7.5 and 8.5 % and their age ranged from 30 to 60 years old. Patients were instructed for life style modification regarding eating and exercise and were given metformin alone with regular follow up of their fasting and post prandial blood glucose monthly and at the end of study HbA1c was repeated and patients are divided into 2 groups (responders and non responders). Genomic DNA extraction and analysis using PCR followed by sequencing analysis of rs2289669 polymorphism in the gene encoding MATE1 (SLC47A1) was done for each patient. Results: The decrease of HbA1c was highest in AA genotype (-0.71+0.26) followed by AG genotype (-0.57+0.35), and lowest found in GG genotype (-0.23+0.3) Conclusion: The rs2289669 G>A polymorphism of the MATE gene was associated with an increased glucose-lowering effect, implying that the gene with the A allele encodes a MATE1 efflux transporter less effective in transporting metformin. |