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

Hoenig, Michel R., Walker, Philip J., Gurnsey, Christine, Beadle, Karen and Johnson, Leslie (2011) The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort. Journal of Clinical Lipidology, 5 2: 91-96. doi:10.1016/j.jacl.2011.01.001

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Author Hoenig, Michel R.
Walker, Philip J.
Gurnsey, Christine
Beadle, Karen
Johnson, Leslie
Title The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort
Formatted title
The C3435T polymorphism in ABCB1 influences atorvastatin efficacy and muscle symptoms in a high-risk vascular cohort
Journal name Journal of Clinical Lipidology
ISSN 1933-2874
Publication date 2011-04-01
Sub-type Article (original research)
DOI 10.1016/j.jacl.2011.01.001
Open Access Status Not yet assessed
Volume 5
Issue 2
Start page 91
End page 96
Total pages 6
Place of publication Philadelphia, PA, U.S.A.
Publisher Elsevier Inc.
Language eng
Subject 2724 Internal Medicine
2712 Endocrinology, Diabetes and Metabolism
2916 Nutrition and Dietetics
2705 Cardiology and Cardiovascular Medicine
Abstract 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.
Keyword ABCB1
Cholesterol
P-glycoprotein
Pharmacogenomics
Statin
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
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