The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort

被引:59
作者
Hoenig, Michel R. [1 ]
Walker, Philip J. [2 ]
Gurnsey, Christine [3 ]
Beadle, Karen [3 ]
Johnson, Leslie [3 ]
机构
[1] Univ Queensland, Royal Brisbane & Womens Hosp, Clin Res Ctr, Herston, Qld 4029, Australia
[2] Univ Queensland, Dept Surg, Brisbane, Qld 4072, Australia
[3] Royal Brisbane & Womens Hosp, Queensland Hlth Pathol Serv, Brisbane, Qld, Australia
基金
英国医学研究理事会;
关键词
ABCB1; Cholesterol; P-glycoprotein; Pharmacogenomics; Statin; MULTIDRUG-RESISTANCE GENE; P-GLYCOPROTEIN EXPRESSION; COA REDUCTASE INHIBITORS; CHOLESTEROL ABSORPTION; STATIN THERAPY; MDR1; ABCB1; VARIANTS; ASSOCIATION; SIMVASTATIN; HAPLOTYPES;
D O I
10.1016/j.jacl.2011.01.001
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
OBJECTIVE: The CC genotype of the C3435T polymorphism in ABCB1 is associated with increased P-glycoprotein expression, reduced low-density lipoprotein cholesterol (LDL-C) response to atorvastatin, and a reduced area-under-the-curve in pharmacokinetic studies. We sought to assess the relationship between 1) genotype and Atorvastatin efficacy, independently of variation in cholesterol metabolism and 2) genotype and myalgia. METHODS: High-risk vascular patients were genotyped and treated with atorvastatin 80 mg for 6 weeks. The lipid panel and percent LDL-C reduction with atorvastatin were related to C3435T genotype. Genotypes and allele frequency were assessed in patients with and without myalgia. RESULTS: A total of 117 patients were recruited and genotyped. Of these, 98 completed the study with adequate atorvastatin adherence, and 10 reported myalgia. T and C allele frequencies were 0.63 and 0.37, respectively. A 6-week course of atorvastatin (80 mg/day) reduced LDL-C by 58% +/- 11% (mean +/- SD). Patients with the CC genotype showed less LDL-C reduction with atorvastatin compared with the TT/TC genotype (53% vs 59%, respectively, P = .034), and this finding was independent of variation in cholesterol metabolism (P = .045 after correction for desmosterol and cholestanol/cholesterol ratio). The T allele was more frequent in patients with myalgia than those without (0.80 vs 0.62) and the C allele less frequent (0.20 vs 0.38, P = .043). CONCLUSION: In patients treated with atorvastatin, the CC genotype at the C3435T polymorphism in ABCB1 is associated with reduced atorvastatin efficacy independently of cholesterol metabolism. The T allele is more frequent and the C allele less frequent in patients with myalgia. 2011 National Lipid Association. All rights reserved.
引用
收藏
页码:91 / 96
页数:6
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