A variant of GRK5 is associated with the therapeutic efficacy of repaglinide in Chinese Han patients with type 2 diabetes mellitus

Drug Dev Res. 2018 May;79(3):129-135. doi: 10.1002/ddr.21426. Epub 2018 Apr 16.

Abstract

Post-Market Research We aimed to investigate the impact of G protein-coupled receptor kinase 5 (GRK5) rs10886471 polymorphism on repaglinide efficacy in Chinese patients with type 2 diabetes mellitus (T2DM). A total of 300 T2DM patients and 210 healthy controls were genotyped for GRK5 rs10886471 on a three-dimensional polyacrylamide gel-based DNA microarray. Eighty-five patients with the same genotypes of cytochrome P450 (CYP) 2C8*3 139Arg and organic anion-transporting polypeptide 1B1 (OATP1B1) 521TT were randomly selected to orally take repaglinide for eight consecutive weeks. Then, the biochemical indicators and pharmacodynamic parameters were measured before and after repaglinide treatment. The T allelic frequency of GRK5 rs10886471 was higher in T2DM patients than in healthy subjects (p < .01). T2DM patients with genotypes CC and CT at GRK5 rs10886471 had a significant reduction in terms of fasting plasma glucose (FPG) compared with those with genotype TT (p < .01). In addition, the carriers of genotypes CC and CT at GRK5 rs10886471 had higher differential values of postprandial serum insulin (PINS) compared with genotype TT carriers (p < .05). These findings suggest that GRK5 rs10886471 polymorphism may influence the therapeutic efficacy of repaglinide in Chinese Han T2DM patients.

Keywords: GRK5 rs10886471; polymorphism; repaglinide; therapeutic efficacy; type 2 diabetes mellitus; variant.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Asian People
  • Blood Glucose / drug effects
  • Carbamates / therapeutic use*
  • Cytochrome P-450 CYP2C8 / genetics
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • G-Protein-Coupled Receptor Kinase 5 / genetics*
  • Genotype
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Liver-Specific Organic Anion Transporter 1 / genetics
  • Male
  • Middle Aged
  • Piperidines / therapeutic use*
  • Polymorphism, Genetic
  • Treatment Outcome

Substances

  • Blood Glucose
  • Carbamates
  • Hypoglycemic Agents
  • Insulin
  • Liver-Specific Organic Anion Transporter 1
  • Piperidines
  • SLCO1B1 protein, human
  • repaglinide
  • CYP2C8 protein, human
  • Cytochrome P-450 CYP2C8
  • G-Protein-Coupled Receptor Kinase 5
  • GRK5 protein, human