title: [Genetic marker of statin-induced rhabdomyolysis].
abstract: This review summarizes genetic factors predisposed to statin-induced rhabdomyolysis. The first genetic risk factor of statin myopathy uncovered by genome-wide analysis of single nucleotide polymorphisms was the common variant of SLCO1B1 gene. Analysis of 30000 genetic markers in 85 patients with myopathy induced by high-dose simvastatin showed a strong association with 521T>C polymorphism of SLCO1B1. Another study also showed that this variant of SLCO1B1 has a significant association with myopathy in patients taking pravastatin or atorvastatin although the number of patients analyzed was limited. In addition to SLCO1B1, recent studies suggested that variants of genes encoding transporters (ABCG2 and ABCB1) and metabolic enzymes (CYP2C8 and UGT1A3) involved in the disposition of statins, and those involved in the metabolic muscle disease (glycogen storage disorders, carnitine palmitoyl-2 deficiency and myoadenylate deaminase deficiency) are also risk factors of statin-induced myopathy. These genetic factors may provide predisposition testing for statin-induced rhabdomyolysis.
authors.affiliation: Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Chiba University. kchiba@p.chiba-u.ac.jp
authors.forename: Kan
authors.initials: K
authors.lastname: Chiba
authors.forename: Kaori
authors.initials: K
authors.lastname: Morimoto
mesh_terms: D000659:AMP Deaminase / Q000172:deficiency; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D002334:Carnitine O-Palmitoyltransferase / Q000172:deficiency; D065727:Cytochrome P-450 CYP2C8; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D014453:Glucuronosyltransferase / Q000235:genetics; D006008:Glycogen Storage Disease; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects*; D027381:Liver-Specific Organic Anion Transporter 1; D008661:Metabolism, Inborn Errors; D009363:Neoplasm Proteins / Q000235:genetics; D027361:Organic Anion Transporters / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012206:Rhabdomyolysis / Q000139:chemically induced* / Q000235:genetics*; D012307:Risk Factors; D019821:Simvastatin / Q000009:adverse effects
chemical_list: C513055:ABCB1 protein, human; C116614:ABCG2 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; 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; D019821:Simvastatin; D001189:Aryl Hydrocarbon Hydroxylases; C450259:CYP2C8 protein, human; D065727:Cytochrome P-450 CYP2C8; D002334:Carnitine O-Palmitoyltransferase; C122075:UDP-glucuronosyltransferase, UGT1A3; D014453:Glucuronosyltransferase; D000659:AMP Deaminase