A Common Susceptibility Gene for Type 2 Diabetes Is Associated with Drug Response to a DPP-4 Inhibitor: Pharmacogenomic Cohort in Okinawa Japan

PLoS One. 2016 May 3;11(5):e0154821. doi: 10.1371/journal.pone.0154821. eCollection 2016.

Abstract

We investigated the association between common type 2 susceptibility variants of CDK5 regulatory subunit associated protein 1-like 1(CDKAL1) and therapeutic responses to anti-diabetic agents among patients with type 2 diabetes. Two SNPs (rs7754840: C>G, rs7756992: A>G) were genotyped via the Taqman PCR method. A total of 798 type 2 diabetic patients were included. HbA1c reduction after use of DPP-4 inhibitors for 3 months was significantly greater in patients with a risk allele for type 2 diabetes (GG -0.4%, CG -0.5%, CC -0.8%, p = 0.02 for rs7754840 and AA -0.4%, AG -0.5%, GG -0.8%, p = 0.01 for rs7756992). Linear regression analysis showed that per allele reductions of hemoglobin A1c (HbA1c) after 3 months were -0.10% for rs7754840 (p = 0.02) and -0.13% for rs7756992 (p = 0.0008) after adjusting for clinically influential covariates such as age, sex, BMI, duration of diabetes, baseline HbA1c and concomitant anti-diabetic agents. The results suggested that common variants of CDKAL1 are associated with therapeutic response to DPP-4 inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Dipeptidyl-Peptidase IV Inhibitors / pharmacology*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genomics
  • Glycated Hemoglobin / metabolism
  • Humans
  • Japan
  • Male
  • Middle Aged
  • Pharmacogenetics
  • Treatment Outcome
  • tRNA Methyltransferases / genetics*

Substances

  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • hemoglobin A1c protein, human
  • tRNA Methyltransferases
  • CDKAL1 protein, human

Grants and funding

This work was supportd by Japan Research Foundation for Clinical Pharmacology, Strategic Research Promotion Unit of University of the Ryukyus. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.