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- Title
Association between statin-induced creatine kinase elevation and genetic polymorphisms in SLCO1B1, ABCB1 and ABCG2.
- Authors
Ferrari, Marco; Guasti, Luigina; Maresca, Andrea; Mirabile, Mauro; Contini, Sara; Grandi, Anna; Marino, Franca; Cosentino, Marco
- Abstract
Purpose: Treatment with statins requires close monitoring of serum creatine kinase (CK) levels to prevent myopathy, a common and potentially serious dose-dependent adverse effect of these drugs. We have investigated the correlation between elevated CK levels and polymorphisms in the genes encoding transporters involved in statin disposition. Methods: Patients with and without statin-induced elevated serum CK levels were genotyped for polymorphisms in SLCO1B1 ( SLCO1B1 A388G and SLCO1B1 T521C), ABCB1 ( ABCB1 C1236T and ABCB1 C3435T) and ABCG2 ( ABCG2 C421A). Results: Patients carrying SLCO1B1 T521C or ABCB1 C1236T single nucleotide polymorphisms (SNPs) had an odds ratio (OR) for statin-induced elevated serum CK levels of 8.86 ( p < 0.01) and 4.67 ( p < 0.05), respectively, while patients carrying the SLCO1B1 A388G SNP had an OR of 0.24 ( p < 0.05). An arbitrary score based on genotype combination discriminated patients with and without CK elevation at a specificity of 97 % and a sensitivity of 39 %. Conclusion: Genotyping of the SLCO1B1, ABCB1 and ABCG2 genes deserves consideration as a clinical approach to improve statin safety while concomitantly reducing the burden of blood tests for CK measurements.
- Subjects
ITALY; ACADEMIC medical centers; ANALYSIS of variance; CHI-squared test; CONFIDENCE intervals; CREATINE kinase; EPIDEMIOLOGY; FISHER exact test; GENETIC polymorphisms; REGRESSION analysis; U-statistics; STATINS (Cardiovascular agents); DATA analysis; CASE-control method; RECEIVER operating characteristic curves; STATISTICAL models; DESCRIPTIVE statistics
- Publication
European Journal of Clinical Pharmacology, 2014, Vol 70, Issue 5, p539
- ISSN
0031-6970
- Publication type
Article
- DOI
10.1007/s00228-014-1661-6