@article {Chen:2008:1107-3756:345,
title = "Analysis of polymorphisms in the 3' untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response",
journal = "International Journal of Molecular Medicine",
parent_itemid = "infobike://sp/ijmm",
publishercode ="sp",
year = "2008",
volume = "21",
number = "3",
publication date ="2008-01-01T00:00:00",
pages = "345-353",
itemtype = "ARTICLE",
issn = "1107-3756",
eissn = "1791-244X",
url = "https://www.ingentaconnect.com/content/sp/ijmm/2008/00000021/00000003/art00010",
author = "Chen, Wei and Wang, Shukui and Ma, Yuling and Zhou, Yue and Liu, Haiyan and Strnad, Pavel and Kraemer, Fredric B. and Krauss, Ronald M. and Liu, Jingwen",
abstract = "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.",
}