Genetic Variants Identified from GWAS for Predisposition to Type 2 Diabetes Predict Sulfonylurea Drug Response

Background: Several SNPs were identified through GWAS for their association with type 2 diabetes which has implications to pancreatic β-cell physiology. Objective: We aimed to study the role of risk alleles of TCF7L2, KCNJ11, CDKN2A, CDKAL1, IGF2BP2, SLC30A8 and KCNQ1 along with pharmacokinetic variants in response to sulfonylureas. Method: We performed a prospective study on 209 newly diagnosed subjects; treatment naive T2D subjects were recruited. Individuals were started with glibenclamide monotherapy and followed-up for 12 weeks. Genotyping was done, using PCR-RFLP and TETRA-ARMS PCR and confirmed by DNA sequencing. Results: In univariate regression analysis, KCNJ11 (rs5219) was only the predictor for glibenclamide treatment failure. Conclusion: The present data suggests a possible role of KCNJ11 gene in altered response to glibenclamide.