Analysis of polymorphisms in the 3' untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response

  • Authors:
    • Wei Chen
    • Shukui Wang
    • Yuling Ma
    • Yue Zhou
    • Haiyan Liu
    • Pavel Strnad
    • Fredric B. Kraemer
    • Ronald M. Krauss
    • Jingwen Liu
  • View Affiliations

  • Published online on: March 1, 2008     https://doi.org/10.3892/ijmm.21.3.345
  • Pages:345-353
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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.

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March 2008
Volume 21 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

2016 Impact Factor: 2.341
Ranked #21/128 Medicine Research and Experimental
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APA
Chen, W., Wang, S., Ma, Y., Zhou, Y., Liu, H., Strnad, P. ... Liu, J. (2008). Analysis of polymorphisms in the 3' untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response. International Journal of Molecular Medicine, 21, 345-353. https://doi.org/10.3892/ijmm.21.3.345
MLA
Chen, W., Wang, S., Ma, Y., Zhou, Y., Liu, H., Strnad, P., Kraemer, F. B., Krauss, R. M., Liu, J."Analysis of polymorphisms in the 3' untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response". International Journal of Molecular Medicine 21.3 (2008): 345-353.
Chicago
Chen, W., Wang, S., Ma, Y., Zhou, Y., Liu, H., Strnad, P., Kraemer, F. B., Krauss, R. M., Liu, J."Analysis of polymorphisms in the 3' untranslated region of the LDL receptor gene and their effect on plasma cholesterol levels and drug response". International Journal of Molecular Medicine 21, no. 3 (2008): 345-353. https://doi.org/10.3892/ijmm.21.3.345