Effects of ABCA1 variants on rosiglitazone monotherapy in newly diagnosed type 2 diabetes patients

Acta Pharmacol Sin. 2008 Feb;29(2):252-8. doi: 10.1111/j.1745-7254.2008.00744.x.

Abstract

Aim: The aim of the present study was to investigate the relationship between R219K, M883I, and R1587K variants of the ATP-binding cassette transporter subfamily A number 1 (ABCA1) gene and response to rosiglitazone treatment in newly diagnosed patients with type 2 diabetes.

Methods: A total of 105 diabetic patients with no history of antihyperglycemia medication were treated with rosiglitazone (4 or 8 mg daily) for 48 weeks. Three non-synonymous variants R219K, M883I, and R1587K, were genotyped in all patients.

Results: Ninety-three patients completed the entire study. The R219K variant of ABCA1 had an effect on rosiglitazone response with the per-allele odds ratio of 2.04 for treatment failure (P<0.05). The RR homozygotes had a better improvement in indicators of insulin sensitivity, as determined by a significantly greater decrease in the homeostasis model assessment index of insulin resistance (-2.39+/-0.46 vs -0.69+/-0.51, P<0.05). No genotype-phenotype association was detected for M883I and R1587K.

Conclusion: The R219K variant of ABCA1 was associated with the therapeutic effect of rosiglitazone. The RR homozygotes had a better response to rosiglitazone treatment in terms of insulin sensitivity improvement than minor K allele carriers. Neither the M883I nor R1587K variant of the ABCA1 gene was associated with rosiglitazone response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics*
  • Adult
  • Aged
  • Body Mass Index
  • DNA / genetics
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / genetics*
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Middle Aged
  • Rosiglitazone
  • Thiazolidinediones / therapeutic use*
  • Waist-Hip Ratio

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Rosiglitazone
  • DNA