title: No effect of CYP3A4 intron 6 C>T polymorphism (CYP3A4*22) on lipid-lowering response to statins in Greek patients with primary hypercholesterolemia.
abstract: BACKGROUND
  Interindividual variability exists in statin lipid-lowering response, partially attributed to genetic factors. CYP3A4 intron 6 C>T polymorphism (CYP3A4*22 allele, rs35599367) has been recently identified and was associated with reduced CYP3A4 expression. We analyzed the association of CYP3A4*22 allele with response to atorvastatin and simvastatin.
  
  
  METHODS
  A total of 416 statin-treated (207 atorvastatin- and 209 simvastatin-treated) adults with primary hypercholesterolemia were included in the study. Total cholesterol and low-density lipoprotein cholesterol were measured at baseline and on 6 months of treatment. CYP3A4*22 allele was analyzed with TaqMan assay.
  
  
  RESULTS
  In the entire cohort population, 41 individuals carried CYP3A4*22 allele (18 in atorvastatin and 23 in simvastatin treatment). CYP3A4*22 allele was not associated with lipid-lowering response to atorvastatin or simvastatin. No sex-gene or statin dose-gene interaction was observed in either statin-treated patient cohort.
  
  
  CONCLUSIONS
  The effect of CYP3A4*22 allele on lipid-lowering response to CYP3A metabolized statins, if present, can potentially be masked by relevant confounding or uncontrolled factors; therefore, further population-driven studies are required.
authors.forename: Georgia
authors.initials: G
authors.lastname: Ragia
authors.forename: Vana
authors.initials: V
authors.lastname: Kolovou
authors.forename: Anna
authors.initials: A
authors.lastname: Tavridou
authors.forename: Laure
authors.initials: L
authors.lastname: Elens
authors.forename: Alexandros D
authors.initials: AD
authors.lastname: Tselepis
authors.forename: Moses
authors.initials: M
authors.lastname: Elisaf
authors.forename: Ron H N
authors.initials: RH
authors.lastname: Van Schaik
authors.forename: Genovefa
authors.initials: G
authors.lastname: Kolovou
authors.forename: Vangelis G
authors.initials: VG
authors.lastname: Manolopoulos
mesh_terms: D000069059:Atorvastatin / Q000008:administration & dosage*; D002784:Cholesterol / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D015331:Cohort Studies; D051544:Cytochrome P-450 CYP3A / Q000235:genetics*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005787:Gene Frequency; D006115:Greece / Q000208:ethnology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics; D007438:Introns / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics*; D019821:Simvastatin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol; D000069059:Atorvastatin; D019821:Simvastatin; D051544:Cytochrome P-450 CYP3A