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

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.

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Corresponding author

Correspondence to Wei-ping Jia.

Additional information

Project supported by the National 973 Program (No 2006CB503901) and the Key Project of the Science and Technology Commission of Shanghai Municipality (No 01ZD002).

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Wang, J., Bao, Yq., Hu, C. et al. Effects of ABCA1 variants on rosiglitazone monotherapy in newly diagnosed type 2 diabetes patients. Acta Pharmacol Sin 29, 252–258 (2008). https://doi.org/10.1111/j.1745-7254.2008.00744.x

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Keywords

  • pharmacogenetics
  • rosiglitazone
  • ATP-binding cassette transporter subfamily A number 1
  • single nucleotide polymorphisms

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