ABCMdb

PMID: 18215356

Wang J, Bao YQ, Hu C, Zhang R, Wang CR, Lu JX, Jia WP, Xiang KS
Effects of ABCA1 variants on rosiglitazone monotherapy in newly diagnosed type 2 diabetes patients.
Acta Pharmacol Sin. 2008 Feb;29(2):252-8., [PubMed]

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No. Mutations Sentence Comment

0 ABCA1 p.Arg219Lys (c)2008 CPS and SIMM Acta Pharmacol Sin 2008 Feb; 29 (2): 252-258 Full-lengtharticle 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 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 subfamilyA number 1 (ABCA1) gene and response to rosiglitazone treatment in newly diagnosed patients with type 2 diabetes. Login to comment 2 ABCA1 p.Arg219Lys Three non-synonymous variants R219K, M883I, and R1587K, were genotyped in all patients. Login to comment 4 ABCA1 p.Arg219Lys The R219K variant of ABCA1had an effect on rosiglitazone response with the per-allele odds ratio of 2.04 for treatment failure (P<0.05). Login to comment 7 ABCA1 p.Arg219Lys Conclusion: The R219K variant ofABCA1was associated with the therapeutic effect ofrosiglitazone. Login to comment 32 ABCA1 p.Arg219Lys In this study, we selected 3 non-synonymous variants of ABCA1, R219K, M883I, and R1587K, toevaluate their effects on rosiglitazone treatment in newly diagnosed patients with type 2 diabetes. Login to comment 88 ABCA1 p.Arg219Lys Pairwise linkage disequilibrium analyses among ABCA1 gene R219K, M883I and R1587K variants. Login to comment 89 ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys ABCA1 p.Arg219Lys | D´| \r2 R219K M883I R1587K R219K 0.041 0.027 M883I 0.372 0.031 R1587K 0.191 0.377 Linkage disequilibrium estimates are shown as |D´| in the lower triangle and r2 in the upper triangle. Login to comment 91 ABCA1 p.Arg219Lys According to the first criterion, R219K was associated with response to rosiglitazone treatment with more treatment failures in the rare allele homozygotes KK. Login to comment 97 ABCA1 p.Arg219Lys Association between ABCA1 genetic variants and the effect of rosiglitazone treatment on clinical features The association between R219K and clinical features is shown in Table 4. Login to comment 106 ABCA1 p.Arg219Lys In this study, we found that the R219K variant of the ABCA1 gene was associated with response to rosiglitazone therapy in newly diagnosed type 2 diabetes patients. Login to comment 113 ABCA1 p.Arg219Lys The main outcome of our study was that R219K was associated with insulin sensitivityimprovement. Login to comment 119 ABCA1 p.Arg219Lys Criterion 1 Criterion 2 R219K RR RK KK RR RK KK Responder 14 (0.483) 19 (0.452) 2 (0.118) 24 (0.889) 33 (0.767) 11 (0.647) Non-responderb 15 (0.517) 23 (0.548) 15 (0.882) 3 (0.111) 10 (0.233) 6 (0.353) M883I MM MI II MM MI II Responder 15 (0.319) 15 (0.455) 5 (0.625) 33 (0.717) 29 (0.878) 6 (0.750) Non-responder 32 (0.681) 18 (0.545) 3 (0.375) 13 (0.283) 4 (0.121) 2 (0.250) R1587K RR RK KK RR RK KK Responder 13 (0.394) 18 (0.400) 4 (0.400) 26 (0.788) 37 (0.822) 5 (0.556) Non-responder 20 (0.606) 27 (0.600) 6 (0.600) 7 (0.212) 8 (0.178) 4 (0.444) pose that a small change in ABCA1 activity could affect rosiglitazone response without markedlyimpacting circulating cholesterol profiles. Login to comment 126 ABCA1 p.Arg219Lys Association between ABCA1 R219K variant and clinical features. Login to comment 130 ABCA1 p.Arg219Lys The K allele carriers of the R219K variant showed a relatively higher mean drug dose compared with the RR homozygotes, which may also reflect a poorer response torosiglitazone treatment. Login to comment 133 ABCA1 p.Arg219Lys In conclusion, we provide evidence that the R219K variant of the ABCA1 gene either directly or as a marker with additional functional variant in linkage disequilibrium, has an effect on response torosiglitazone treatment. Login to comment