title: CYP7A1 polymorphism influences the LDL cholesterol-lowering response to atorvastatin.
abstract: OBJECTIVE
  Response to the lipid-lowering effect of the statins is known to show significant inter-individual variability. Our aim was to investigate whether genetic variants of the CYP3A5 gene, CYP7A1 gene and ABCG8 gene influence the lipid-lowering response to atorvastatin.
  
  
  METHODS
  One hundred and seven unrelated Chinese Han hypercholesterolemia patients were recruited from among the inpatients and outpatients of Tangshan Gongren Hospital of Hebei, China. Three polymorphisms of the CYP3A5 gene, seven polymorphisms of the CYP7A1 gene and seven polymorphisms of the ABCG8 gene were selected using a tagging single-nucleotide polymorphism (tSNP) strategy and genotyped using Snapshot platform.
  
  
  RESULTS
  SNP rs8192870, located in the first intron of the CYP7A1 gene, was associated with the LDL level lowering response to atorvastatin. The LDL levels were reduced by 27.89% for the GG/GA genotype carriers and 35.26% for the AA genotype carriers, respectively, after atorvastatin treatment (P = 0.021). The significance remained after adjusting for covariates. In addition, we observed that rs4148222 in the 11th intron of the ABCG8 gene significantly associated with the baseline levels of HDL (P = 0.046).
  
  
  CONCLUSIONS
  CYP7A1 gene polymorphism influences the LDL-lowering effects of atorvastatin in Chinese Hans. If replicated by others, identification of the tagged functional variant would be needed.
authors.affiliation: Key Laboratory for Basic Research in Cardiovascular Science, Ministry of Education, Tongji University School of Medicine, Shanghai, China.
authors.forename: X-Y
authors.initials: XY
authors.lastname: Jiang
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
authors.forename: P
authors.initials: P
authors.lastname: Chen
authors.forename: S-Y
authors.initials: SY
authors.lastname: Li
authors.forename: N-N
authors.initials: NN
authors.lastname: Zhang
authors.forename: X-D
authors.initials: XD
authors.lastname: Chen
authors.forename: G-C
authors.initials: GC
authors.lastname: Wang
authors.forename: H-B
authors.initials: HB
authors.lastname: Wang
authors.forename: M-Q
authors.initials: MQ
authors.lastname: Zhuang
authors.forename: M
authors.initials: M
authors.lastname: Lu
mesh_terms: D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000368:Aged; D000069059:Atorvastatin; D002681:China; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood / Q000187:drug effects*; D051544:Cytochrome P-450 CYP3A / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D006937:Hypercholesterolemia / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011758:Pyrroles / Q000494:pharmacology*
chemical_list: C416946:ABCG8 protein, human; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C553219:CYP7A1 protein, human; D002790:Cholesterol 7-alpha-Hydroxylase