Acta Pharmacologica Sinica 2008 February; 29 (2): 252-258; doi: 10.1111/j.1745-7254.2008.00744.x

 
Original Article
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Effects of ABCA1 variants on rosiglitazone monotherapy in newly diagnosed type 2 diabetes patients1
 

Jie WANG2, Yu-qian BAO2, Cheng HU2, Rong ZHANG2, Cong-rong WANG2, Jun-xi LU2, Wei-ping JIA2,3, Kun-san XIANG2

Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China

 

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.

 

Keywords: pharmacogenetics; rosiglitazone; ATP-binding cassette transporter subfamily A number 1; single nucleotide polymorphisms

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

3 Correspondence to Dr Wei-ping JIA.
Phn 86-21-6436-9181, ext 8922.
Fax 86-21-6436-8031.
E-mail wpjia@sjtu.edu.cn
Received 2007-08-11     Accepted 2007-10-10

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