Abstract:
:The mixed dyslipidemia phenotype is characterized by elevated triglycerides (TG), low HDL cholesterol (HDL-C), increased ApoB levels, and premature coronary atherosclerosis. Fibrate-statin combination therapy reduces ApoB levels and coronary events in the mixed dyslipidemia population. We sought to identify gene-gene interactions that affect ApoB response to statin-fenofibric acid therapy in the mixed dyslipidemia population. Using a predefined subset of single-nucleotide polymorphisms (SNPs) that were previously associated with TG, VLDL, or HDL-C, we applied gene-gene interaction testing in a randomized, double-blind, clinical trial examining the response to fenofibric acid (FNA) and its combination with statin in 1,865 individuals with mixed dyslipidemia. Of 11,783 possible SNP pairs examined, we detected a single significant interaction between rs12130333, located within the ANGPTL3 gene region, and rs4240705, within the RXRA gene, on ApoB reduction after statin-FNA therapy (P = 4.0 × 10(-6)). ApoB response to therapy gradually reduced with the increasing number of T alleles in the rs12130333 but only in the presence of the GG genotype of rs4240705. Individuals doubly homozygous for the minor alleles at rs12130333 and rs4240705 showed a paradoxical increase of 1.8% in ApoB levels after FNA-statin combination therapy. No gene-gene interaction was identified other than an interaction between SNPs in the ANGPTL3 and RXRA regions, which results in the inhibition of ApoB reduction in response to statin-FNA therapy. Further study is required to examine the clinical applicability of this genetic interaction and its effect on coronary events.
journal_name
J Lipid Resjournal_title
Journal of lipid researchauthors
Ma L,Ballantyne CM,Belmont JW,Keinan A,Brautbar Adoi
10.1194/jlr.M028829subject
Has Abstractpub_date
2012-11-01 00:00:00pages
2425-8issue
11eissn
0022-2275issn
1539-7262pii
jlr.M028829journal_volume
53pub_type
杂志文章,随机对照试验abstract::We studied the biogenesis of apolipoprotein B (apoB) in primary hepatocytes isolated from hamster liver, an animal model with striking resemblance to humans in lipoprotein metabolism. Hamster hepatocytes were found to assemble and secrete apoB-containing lipoproteins at a density of VLDL. Intracellular mechanisms of a...
journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:1996-01-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
doi:
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:1982-01-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:1991-08-01 00:00:00
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journal_title:Journal of lipid research
pub_type: 杂志文章
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更新日期:1998-03-01 00:00:00
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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pub_type: 杂志文章
doi:
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
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journal_title:Journal of lipid research
pub_type: 杂志文章
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