title: Association between statin-induced creatine kinase elevation and genetic polymorphisms in SLCO1B1, ABCB1 and ABCG2.
abstract: OBJECTIVE
  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 %.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Center of Research in Medical Pharmacology, University of Insubria, Via Ottorino Rossi n. 9, 21100, Varese, VA, Italy, marco.ferrari@uninsubria.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Ferrari
authors.forename: Luigina
authors.initials: L
authors.lastname: Guasti
authors.forename: Andrea
authors.initials: A
authors.lastname: Maresca
authors.forename: Mauro
authors.initials: M
authors.lastname: Mirabile
authors.forename: Sara
authors.initials: S
authors.lastname: Contini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Grandi
authors.forename: Franca
authors.initials: F
authors.lastname: Marino
authors.forename: Marco
authors.initials: M
authors.lastname: Cosentino
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D016022:Case-Control Studies; D003402:Creatine Kinase / Q000097:blood*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D014018:Tissue Distribution / Q000235:genetics
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D009363:Neoplasm Proteins; D027361:Organic Anion Transporters; C503999:SLCO1B1 protein, human; D003402:Creatine Kinase