title: The effect of CYP7A1 polymorphisms on lipid responses to fenofibrate.
abstract: BACKGROUND
  CYP7A1 encodes cholesterol 7α-hydroxylase, an enzyme crucial to cholesterol homeostasis. Its transcriptional activity is downregulated by fenofibrate. The goal of this study was to determine the effect of CYP7A1 polymorphisms on lipid changes in response to fenofibrate.
  
  
  METHODS
  We examined the associations of 3 tagging single nuclear polymorphisms (i6782C>T, m204T>G, 3U12536A>C) at CYP7A1 with triglyceride (TG) and high-density lipoprotein cholesterol (HDL)-C responses to a 3-week treatment with 160 mg/d of fenofibrate in 864 US white participants from the Genetics of Lipid Lowering Drugs and Diet Network study.
  
  
  RESULTS
  The m204T>G variant was significantly associated with TG and HDL-C responses with fenofibrate. Individuals homozygous for the common T allele of m204T>G single nuclear polymorphism displayed both the greater reduction of TG (-32% for TT, -28% for GT, -25% for GG, P = 0.004) and an increase of HDL-C response compared with noncarriers (4.1% for TT, 3.4% for GT, 1.2% for GG, P = 0.01). Conversely, individuals homozygous for the minor allele of i6782C>T showed a greater increase in the HDL-C response compared with noncarriers (2.8% CC, 4.5% for CT, 5.8% for TT, P = 0.02), albeit no significant effect on TG response.
  
  
  CONCLUSIONS
  Our data suggest that common variants at the CYP7A1 locus modulate the TG-lowering and HDL-C-raising effects of fenofibrate, and contribute to the interindividual variation of the drug responses.
authors.affiliation: Bone and Mineral Unit, Division of Endocrinology, Oregon Health and Science University, Portland, OR 97239, USA. shenjia@ohsu.edu
authors.forename: Jian
authors.initials: J
authors.lastname: Shen
authors.forename: Donna K
authors.initials: DK
authors.lastname: Arnett
authors.forename: Laurence D
authors.initials: LD
authors.lastname: Parnell
authors.forename: Chao-Qiang
authors.initials: CQ
authors.lastname: Lai
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Straka
authors.forename: Paul N
authors.initials: PN
authors.lastname: Hopkins
authors.forename: Ping
authors.initials: P
authors.lastname: An
authors.forename: Mary F
authors.initials: MF
authors.lastname: Feitosa
authors.forename: José M
authors.initials: JM
authors.lastname: Ordovás
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002790:Cholesterol 7-alpha-Hydroxylase / Q000235:genetics*; D008076:Cholesterol, HDL / Q000097:blood; D005260:Female; D011345:Fenofibrate / Q000494:pharmacology*; D014644:Genetic Variation; D006720:Homozygote; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000097:blood; D044465:White People / Q000235:genetics
chemical_list: D008076:Cholesterol, HDL; D000960:Hypolipidemic Agents; D014280:Triglycerides; C553219:CYP7A1 protein, human; D002790:Cholesterol 7-alpha-Hydroxylase; D011345:Fenofibrate
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