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

Curr Mol Med. 2017;17(8):580-586. doi: 10.2174/1566524018666180222122653.

Abstract

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.

Keywords: Genome Wide Association Studies (GWAS); Glibenclamide; KCNJ11 gene.; Sulfonylurea; T-ARMSPCR; Type 2 Diabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes Mellitus, Type 2 / pathology
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Glyburide / pharmacology*
  • Humans
  • Hypoglycemic Agents / pharmacology*
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Insulin-Secreting Cells / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Potassium Channels, Inwardly Rectifying / genetics*
  • Prospective Studies
  • Young Adult

Substances

  • Hypoglycemic Agents
  • Kir6.2 channel
  • Potassium Channels, Inwardly Rectifying
  • Glyburide