| Common variants of HMGCR, CETP, APOAI, ABCB1, CYP3A4, and CYP7A1 genes as predictors of lipid-lowering response to atorvastatin therapy. | |
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MedLine Citation:
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PMID: 20578904 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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There is interindividual variation in lipid-lowering response to statins. The objective of this study was to investigate whether common variation in genes involved in lipid and statin metabolism modify the effect of statins on serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol concentration in coronary artery disease (CAD) patients. We studied the association between 18 single-nucleotide polymorphisms (SNPs) in six genes (HMGCR, CETP, APOAI, ABCB1, CYP3A4, CYP7A1) in response to atorvastatin therapy (20 mg/day) in 265 newly diagnosed CAD patients using multivariable adjusted general linear regression. Variant alleles of ABCB1 (-41A/G), HMGCR SNP29 G/T, rs5908A/G, rs12916C/T, and CYP7A1-204A/C polymorphisms were significantly associated with attenuated LDL-C reduction and variant alleles of CETP TaqI, -629C/A, and APOAI PstI polymorphisms were associated with higher increase in high-density lipoprotein-cholesterol. A three-loci interaction model consisting of CYP7A1rs892871AA/APOAIPstIP1P1/HMGCR rs12916CT was a better predictor for LDL-C lowering, when compared with single polymorphisms analysis on statin response. Variant genotypes of APOAI -2500C/T, CETP 405I/V, and ABCB1 3435C/T showed higher risk of myocardial infarction events (p < 0.05) in a 1-year follow-up of CAD patients. These results suggest that SNPs in lipid and statin pathway genes are associated with reduced LDL-C lowering by statins and identify individuals who may be resistant to maximal LDL-C lowering by statins. |
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Authors:
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Aruna Poduri; Madhu Khullar; Ajay Bahl; B S Sehrawat; Yashpaul Sharma; Kewal K Talwar |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: DNA and cell biology Volume: 29 ISSN: 1557-7430 ISO Abbreviation: DNA Cell Biol. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-09-30 Completed Date: 2010-11-04 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9004522 Medline TA: DNA Cell Biol Country: United States |
Other Details:
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Languages: eng Pagination: 629-37 Citation Subset: IM |
Affiliation:
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Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adult Alleles* Apolipoprotein A-I / genetics* Cholesterol 7-alpha-Hydroxylase Cholesterol Ester Transfer Proteins / genetics Cholesterol, HDL / blood, genetics Cholesterol, LDL / blood, drug effects, genetics Coronary Artery Disease / genetics Cytochrome P-450 CYP3A / genetics* Cytochrome P-450 Enzyme System / genetics Female Genotype Heptanoic Acids / therapeutic use* Humans Hydroxymethylglutaryl CoA Reductases Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use* Lipids / blood*, genetics Male Middle Aged Myocardial Infarction / genetics P-Glycoprotein / genetics* Polymorphism, Single Nucleotide* Pyrroles / therapeutic use* Triglycerides / blood |
| Chemical | |
Reg. No./Substance:
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0/ABCB1 protein, human; 0/Apolipoprotein A-I; 0/CETP protein, human; 0/Cholesterol Ester Transfer Proteins; 0/Cholesterol, HDL; 0/Cholesterol, LDL; 0/Heptanoic Acids; 0/Hydroxymethylglutaryl-CoA Reductase Inhibitors; 0/Lipids; 0/P-Glycoprotein; 0/Pyrroles; 0/Triglycerides; 110862-48-1/atorvastatin; 9035-51-2/Cytochrome P-450 Enzyme System; EC 1.1.1.-/HMGCR protein, human; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases; EC 1.14.13.17/CYP7A1 protein, human; EC 1.14.13.17/Cholesterol 7-alpha-Hydroxylase; EC 1.14.13.67/CYP3A4 protein, human; EC 1.14.14.1/Cytochrome P-450 CYP3A |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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