Document Detail


Haplotypes in the lipoprotein lipase gene influence high-density lipoprotein cholesterol response to statin therapy and progression of atherosclerosis in coronary artery bypass grafts.
MedLine Citation:
PMID:  16755277     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Lipoprotein lipase (LPL) hydrolyzes circulating triglycerides (TGs). We previously showed that 3'-end haplotypes in the LPL gene influence atherosclerosis and insulin resistance. This study asked whether these LPL haplotypes influence response to lipid-lowering therapy among 829 subjects from the Post-Coronary Artery Bypass Graft trial. Lipid profiles were obtained at baseline and 4-5 years after treatment with lovastatin. Haplotypes were based on 12 SNPs. The fourth most frequent haplotype, 12-4, was associated with a decreased increment in high-density lipoprotein-cholesterol (HDL-C) following treatment. Haplotypes 12-6, 12-7 and 12-8 were each associated with increased HDL-C response to therapy, and haplotype 12-2 with decreased TG response. The most common haplotype, 12-1, was protective against graft worsening or occlusion. Haplotype 12-4 reduced HDL-C response to lovastatin, possibly consistent with our prior observations of this haplotype as predisposing to coronary artery disease. LPL may influence atherosclerosis risk through pleiotropic effects on each aspect of the metabolic syndrome.
Authors:
M O Goodarzi; K D Taylor; M T Scheuner; H J Antoine; X Guo; P K Shah; J I Rotter
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2006-06-06
Journal Detail:
Title:  The pharmacogenomics journal     Volume:  7     ISSN:  1470-269X     ISO Abbreviation:  Pharmacogenomics J.     Publication Date:  2007 Feb 
Date Detail:
Created Date:  2007-02-22     Completed Date:  2007-06-20     Revised Date:  2007-12-03    
Medline Journal Info:
Nlm Unique ID:  101083949     Medline TA:  Pharmacogenomics J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  66-73     Citation Subset:  IM    
Affiliation:
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA 9048, USA. mark.goodarzi@cshs.org
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Alleles
Anticholesteremic Agents / therapeutic use*
Atherosclerosis / drug therapy*,  genetics*,  pathology
Blood Pressure / physiology
Cholesterol, HDL / genetics*
Cohort Studies
Coronary Artery Bypass*
Coronary Restenosis / drug therapy*,  genetics*,  pathology
Disease Progression
Female
Genotype
Haplotypes
Humans
Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use*
Insulin Resistance / genetics
Lipoprotein Lipase / genetics*
Male
Mexican Americans
Middle Aged
Polymorphism, Single Nucleotide
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
HL-28481/HL/NHLBI NIH HHS; HL-69757/HL/NHLBI NIH HHS; RR000425/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Anticholesteremic Agents; 0/Cholesterol, HDL; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; EC 3.1.1.34/Lipoprotein Lipase

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


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