KCNQ1 rs2237895 polymorphism is associated with the therapeutic response to sulfonylureas in Iranian type 2 diabetes mellitus patients

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Next to metformin, sulfonylureas (SUs) are the most secondary prescribed oral anti-diabetic drugs. Thus, understanding the genetic role involved in the pharmacodynamics of these drugs can elucidate a considerable knowledge about personalized treatment in type 2 diabetes. This study aimed to investigate the impact of KCNQ1 variants on the response of sulfonylureas among the type 2 diabetes Iranian patients. 100 patients were recruited with type 2 diabetes who failed to achieve glycemic control with metformin monotherapy and have been under sulfonylureas therapy for 6 months since. Regarding SUs response, 50 responder and 50 nonresponder patients have been selected. KCNQ1 rs2237892(C>T) and rs2237895 (A>C) polymorphisms were determined by restriction fragment length polymorphism (RFLP) and assessed their role on response to the treatment retrospectively. Patients with rs2237895 CC and AC genotypes demonstrated a significant decrement in FBS and HbA1c after treatment over patients with AA genotypes (All P < 0.001). Compared to the A allele, the odds ratio for treatment success between carriers with rs2237895 C allele was 4.22-fold (P < 0.001). Patients with rs2237892 CT heterozygous genotype exhibit a higher reduction rate in HbA1c and FBS than CC homozygotes (P=0.064 and P=0.079, respectively). The rs2237892 T allele carriers showed an odds ratio equals to 2.83-fold over C allele carriers in the responder group compared to the non-responder group (p=0.081). In conclusion, current findings suggest that the KCNQ1 rs2237895 polymorphism is associated with the sulfonylureas response on Iranian type 2 diabetes patients

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