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


CONCLUSIONS
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.
Wang
Jie
J
Shanghai Diabetes Institute, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
Bao
Yu-qian
YQ
Hu
Cheng
C
Zhang
Rong
R
Wang
Cong-rong
CR
Lu
Jun-xi
JX
Jia
Wei-ping
WP
Xiang
Kun-san
KS
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D004247:DNA / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D049629:Waist-Hip Ratio
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D004247:DNA