title: SLCO1B1 haplotypes are not associated with atorvastatin-induced myalgia in Brazilian patients with familial hypercholesterolemia.
abstract: OBJECTIVE
  Recent studies reported the association of SLCO1B1 haplotypes with the development of musculoskeletal side effects during simvastatin use. The aim was to evaluate the pharmacogenetic association of SLCO1B1 haplotypes with atorvastatin-induced myalgia in a sample of individuals on high-dose atorvastatin regimens.
  
  
  METHODS
  One hundred and forty-three patients with familial hypercholesterolemia were followed for at least 12 months while receiving atorvastatin. Genotypes for the rs2306283 (c.A388G) and rs4149056 (c.T521C) polymorphisms were detected by high-resolution melting analysis. These markers form four distinct haplotypes (*1A, *1B, *5 and *15).
  
  
  RESULTS
  During the follow-up period, 14 (9.8%) patients developed myalgia and 16 (11.2%) presented CK levels more than 3 times the upper limit of the normal range. No association of the SLCO1B1 rs2306283 and rs4149056 genotypes or haplotypes with the presence of myalgia or creatine kinase (CK) values was found. Presence of rs2306283 AG + GG genotypes was not associated with increased risks of myalgia or abnormal CK values (OR 2.08, 95% CI 0.62-7.00, p = 0.24 and OR 0.51, 95% CI 0.21-1.26, p = 0.15 respectively). The presence of rs4149056 TC + CC genotypes was also not associated with increased risk of myalgia or abnormal CK values (OR 2.24, 95% CI 0.47-10.72, p = 0.31 and OR 1.51, 95% CI 0.57-3.96, p = 0.41 respectively).
  
  
  CONCLUSIONS
  Our findings reaffirm that the SLCO1B1 genetic risk appears to be greater in those patients receiving simvastatin compared with those receiving atorvastatin. This suggests that the importance of SLCO1B1 haplotypes depends on the specific statin that has been used.
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of Sao Paulo Medical School, Avenue Dr. Enéas de Carvalho Aguiar, 44 Cerqueira César, São Paulo, SP, Brazil CEP 05403-000. pacaleb@usp.br
authors.forename: Paulo Caleb Junior Lima
authors.initials: PC
authors.lastname: Santos
authors.forename: Ana Carolina Moron
authors.initials: AC
authors.lastname: Gagliardi
authors.forename: Márcio Hiroshi
authors.initials: MH
authors.lastname: Miname
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Chacra
authors.forename: Raul Dias
authors.initials: RD
authors.lastname: Santos
authors.forename: Jose Eduardo
authors.initials: JE
authors.lastname: Krieger
authors.forename: Alexandre Costa
authors.initials: AC
authors.lastname: Pereira
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001938:Brazil / Q000453:epidemiology; D005260:Female; D030342:Genetic Diseases, Inborn / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D006239:Haplotypes; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy / Q000453:epidemiology / Q000235:genetics*; D027381:Liver-Specific Organic Anion Transporter 1; D008297:Male; D008875:Middle Aged; D009135:Muscular Diseases / Q000453:epidemiology / Q000235:genetics*; D027361:Organic Anion Transporters / Q000235:genetics*; D011758:Pyrroles / Q000627:therapeutic use*
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D027381:Liver-Specific Organic Anion Transporter 1; D027361:Organic Anion Transporters; D011758:Pyrroles; C503999:SLCO1B1 protein, human; D000069059:Atorvastatin