Source:http://linkedlifedata.com/resource/pubmed/id/18288382
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
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| pubmed:dateCreated |
2008-2-21
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| pubmed:abstractText |
The proximal section of the 3' untranslated region (3'UTR) of LDL receptor (LDLR) mRNA contains important regulatory sequences that control the messenger stability and mediate the cholesterol-lowering drug berberine (BBR)-induced increase in LDLR mRNA half-life. In the present study, we examined whether single nucleotide polymorphisms (SNPs) within this region cause a predisposition to the development of coronary heart disease (CHD) and whether they affect the response to BBR treatment. Genomic DNAs were isolated from peripheral blood of a Chinese cohort of 103 normolipidemic subjects and 94 hyperlipidemic CHD patients. The 1.1-kb proximal fragment of LDLR mRNA 3'UTR was PCR-amplified and sequenced. Six SNPs were detected within this region. Among them, the presence of SNP1 and SNP6 in both study groups showed complete association (r2=1). The frequency of individual SNPs and genotypes did not differ between CHD patients and normolipidemic individuals. Allelic variations did not correlate with total and LDL-cholesterol levels. To examine the effects of genetic variations in 3'UTR on BBR treatment, entire 2.5-kb regions of 3'UTR from three common SNP haplotypes were cloned into a luciferase reporter and the reporter constructs were transfected into HepG2 cells. The expression of reporter genes carrying different haplotypes of LDLR 3'UTR was increased to a similar extent upon BBR treatment. Taken together, these findings suggest that the 3'UTR LDLR polymorphisms commonly found in the Chinese population do not cause a predisposition to the development of CHD, nor do they affect the plasma lipid levels or the cholesterol-lowering effect of BBR.
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| pubmed:grant | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/3' Untranslated Regions,
http://linkedlifedata.com/resource/pubmed/chemical/Berberine,
http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol,
http://linkedlifedata.com/resource/pubmed/chemical/Lipids,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, LDL
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
1107-3756
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
21
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
345-53
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| pubmed:meshHeading |
pubmed-meshheading:18288382-3' Untranslated Regions,
pubmed-meshheading:18288382-Asian Continental Ancestry Group,
pubmed-meshheading:18288382-Base Sequence,
pubmed-meshheading:18288382-Berberine,
pubmed-meshheading:18288382-Cell Line, Tumor,
pubmed-meshheading:18288382-China,
pubmed-meshheading:18288382-Cholesterol,
pubmed-meshheading:18288382-Cohort Studies,
pubmed-meshheading:18288382-DNA Mutational Analysis,
pubmed-meshheading:18288382-Female,
pubmed-meshheading:18288382-Gene Expression Regulation,
pubmed-meshheading:18288382-Gene Frequency,
pubmed-meshheading:18288382-Genes, Reporter,
pubmed-meshheading:18288382-Genetic Predisposition to Disease,
pubmed-meshheading:18288382-Haplotypes,
pubmed-meshheading:18288382-Humans,
pubmed-meshheading:18288382-Linkage Disequilibrium,
pubmed-meshheading:18288382-Lipids,
pubmed-meshheading:18288382-Male,
pubmed-meshheading:18288382-Middle Aged,
pubmed-meshheading:18288382-Molecular Sequence Data,
pubmed-meshheading:18288382-Polymorphism, Single Nucleotide,
pubmed-meshheading:18288382-RNA Stability,
pubmed-meshheading:18288382-Receptors, LDL
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| pubmed:year |
2008
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| pubmed:articleTitle |
Analysis of polymorphisms in the 3' untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response.
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| pubmed:affiliation |
VA Palo Alto Health Care System, Palo Alto, CA 94304, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
|