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 (p0.01) and 4.67 (p0.05), respectively, while patients carrying the SLCO1B1 A388G SNP had an OR of 0.24 (p0.05). 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.

Association between statin-induced creatine kinase elevation and genetic polymorphisms in SLCO1B1, ABCB1 and ABCG2

FERRARI, MARCO;GUASTI, LUIGINA;MARESCA, ANDREA MARIA;GRANDI, ANNA MARIA;MARINO, FRANCA;COSENTINO, MARCO
2014

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 (p0.01) and 4.67 (p0.05), respectively, while patients carrying the SLCO1B1 A388G SNP had an OR of 0.24 (p0.05). 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.
http://link.springer.com/article/10.1007/s00228-014-1661-6
ABCB1; ABCG2; Creatine kinase elevation; Genotyping; SLCO1B1; Statin
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11383/1875322
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