title: No association between CYP3A4*22 and statin effectiveness in reducing the risk for myocardial infarction.
abstract: OBJECTIVE
  Genetic variation has been shown to influence statin response in terms of lowering LDL cholesterol. The recently discovered CYP3A4*22 allele (defined as rs35599367) has been shown to affect statin-induced LDL cholesterol lowering. Our objective was to investigate whether this polymorphism modifies the risk reduction for myocardial infarction (MI) by statins.
  
  
  METHODS
  We analyzed the interaction between the *22 minor allele and statin use in the independent Utrecht Cardiovascular Pharmacogenetics study and Rotterdam Study, using logistic and Cox regression models.
  
  
  RESULTS
  In total, 771 MI cases and 6131 controls were included in the analyses. There was no effect of the CYP3A4*22 allelic status in the studies separately, nor when the estimates from both studies were combined (interaction odds ratio: 1.27; 95% CI: 0.73-2.21; p = 0.40 for carriers of the minor T-allele).
  
  
  CONCLUSIONS
  We found no association of the CYP3A4*22 minor allele (rs35599367) with the effectiveness of statins in reducing MI risk.
authors.affiliation: Division of Pharmacoepidemiology & Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Utrecht, The Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: Leusink
authors.forename: Catherine E
authors.initials: CE
authors.lastname: de Keyser
authors.forename: N Charlotte
authors.initials: NC
authors.lastname: Onland-Moret
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Loes E
authors.initials: LE
authors.lastname: Visser
authors.forename: Bruno H
authors.initials: BH
authors.lastname: Stricker
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: Anthonius
authors.initials: A
authors.lastname: de Boer
authors.forename: Ron H N
authors.initials: RH
authors.lastname: van Schaik
authors.forename: Anke Hilse
authors.initials: AH
authors.lastname: Maitland-van der Zee
mesh_terms: D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D005260:Female; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000235:genetics*; D010597:Pharmacogenetics / Q000379:methods; D012306:Risk
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
keywords: CYP3A4; CYP3A4*22; myocardial infarction; pharmacogenetics; rs35599367; statins