Linked Life Data

15910869

Source:http://linkedlifedata.com/resource/pubmed/id/15910869

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2005-5-24
pubmed:abstractText
Bile-acid biosynthesis is a key determinant of intracellular cholesterol and, in turn, cholesterol synthesis rate in hepatocytes. This suggests that variation in the cholesterol 7alpha-hydroxylase gene (CYP7A1), a key enzyme in bile-acid biosynthesis, may influence the statin response. To test this hypothesis, a promoter polymorphism (A-204C) in CYP7A1 was examined in 324 hypercholesterolemic patients treated with atorvastatin 10mg. The variant C allele was significantly and independently associated with poor LDL cholesterol reductions; -39% in wild type allele homozygotes, -37% in variant allele heterozygotes, and -34% in variant allele homozygotes (p<0.0001 for trend). Differences were more striking in men, and were enhanced by the coexistence of common variants of apolipoprotein E gene (APOE), epsilon2 or epsilon4. In subjects having wild type alleles at both loci, the mean reduction in LDL cholesterol was -40%, while the value in subjects having two CYP7A1 variant alleles and at least one variant APOE allele was -31% (p<0.0001). Combination analysis of these two loci more accurately predicted the achievement of goal LDL cholesterol, than did both single locus analysis. We concluded that the CYP7A1 A-204C promoter variant was associated with poor response to atorvastatin, which were additively enhanced by common variants in another locus, APOE.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0021-9150
pubmed:author
pubmed:issnType
Print
pubmed:volume
180
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
407-15
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:15910869-Aged, pubmed-meshheading:15910869-Anticholesteremic Agents, pubmed-meshheading:15910869-Apolipoproteins E, pubmed-meshheading:15910869-Bile Acids and Salts, pubmed-meshheading:15910869-Cholesterol, LDL, pubmed-meshheading:15910869-Cholesterol 7-alpha-Hydroxylase, pubmed-meshheading:15910869-Double-Blind Method, pubmed-meshheading:15910869-Female, pubmed-meshheading:15910869-Genotype, pubmed-meshheading:15910869-Heptanoic Acids, pubmed-meshheading:15910869-Humans, pubmed-meshheading:15910869-Hypercholesterolemia, pubmed-meshheading:15910869-Lovastatin, pubmed-meshheading:15910869-Male, pubmed-meshheading:15910869-Middle Aged, pubmed-meshheading:15910869-Placebos, pubmed-meshheading:15910869-Polymorphism, Genetic, pubmed-meshheading:15910869-Promoter Regions, Genetic, pubmed-meshheading:15910869-Pyrroles, pubmed-meshheading:15910869-Sex Factors, pubmed-meshheading:15910869-Treatment Outcome
pubmed:year
2005
pubmed:articleTitle
A promoter polymorphism in cholesterol 7alpha-hydroxylase interacts with apolipoprotein E genotype in the LDL-lowering response to atorvastatin.
pubmed:affiliation
Lipid Research Laboratory, Division of Endocrinology Metabolism and Molecular Biology, Tufts-New England Medical Center, Boston, USA. kajinami@kanazawa-med.ac.jp
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Randomized Controlled Trial, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural