Document Detail


Interactions between common genetic polymorphisms in ABCG5/G8 and CYP7A1 on LDL cholesterol-lowering response to atorvastatin.
MedLine Citation:
PMID:  15262185     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Cholesterol excretion by ATP binding cassette transporters G5 and G8 (ABCG5/G8) and bile acid biosynthesis by cholesterol 7alpha-hydroxylase (CYP7A1) are major pathways for the removal of cholesterol into bile. To investigate the interactions between common polymorphisms in ABCG5/G8 and CYP7A1 and statin response, we examined the relationships between five non-synonymous polymorphisms in ABCG5/G8 (Q604E, D19H, Y54C, T400K, and A632V) and a promoter variant in CYP7A1 (A-204C) in 337 hypercholesterolemic patients treated with atorvastatin 10mg. The ABCG8 H19 allele was significantly associated with a greater LDL cholesterol reduction relative to the wild type D19 allele (39.6% versus 36.6%, P = 0.043). This difference was enhanced in non-carriers of the CYP7A1 promoter polymorphism (42.7% versus 38.2%, P = 0.048), and was diminished in accordance with the number of CYP7A1 variant alleles (1.8% in heterozygotes and 0.2% in homozygotes). Combination analysis of these polymorphisms explained a greater percentage of LDL cholesterol response variation (8.5% difference across subgroups) than did single polymorphism analysis (4.2% in CYP7A1 and 3.0% in ABCG8 D19H). The other ABCG5/G8 polymorphisms did not show any significant interactions with the CYP7A1 polymorphism. We conclude that the ABCG8 H19 and CYP7A1 C-204 alleles appear to interact in a dose-dependent manner on atorvastatin response.
Authors:
Kouji Kajinami; Margaret E Brousseau; Jose M Ordovas; Ernst J Schaefer
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Atherosclerosis     Volume:  175     ISSN:  0021-9150     ISO Abbreviation:  Atherosclerosis     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-07-20     Completed Date:  2005-04-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  287-93     Citation Subset:  IM    
Copyright Information:
Copyright 2004 Elsevier Ireland Ltd
Affiliation:
Lipid Research Laboratory, Division of Endocrinology Metabolism and Molecular Biology, Tufts-New England Medical Center, Boston, MA, USA. kajinami@kanazawa-med.ac.jp
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MeSH Terms
Descriptor/Qualifier:
ATP-Binding Cassette Transporters / genetics*
Aged
Cholesterol 7-alpha-Hydroxylase / genetics*
Cholesterol, LDL / blood,  drug effects*
Female
Heptanoic Acids / pharmacology*,  therapeutic use
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*,  therapeutic use
Hypercholesterolemia / drug therapy,  genetics
Lipoproteins / genetics*
Male
Middle Aged
Polymorphism, Genetic / genetics*
Pyrroles / pharmacology*,  therapeutic use
Randomized Controlled Trials as Topic
Treatment Outcome
Grant Support
ID/Acronym/Agency:
HL54776/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/ABCG5 protein, human; 0/ABCG8 protein, human; 0/ATP-Binding Cassette Transporters; 0/Cholesterol, LDL; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Lipoproteins; 0/Pyrroles; 110862-48-1/atorvastatin; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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