Title | Quantitative effects of common genetic variations in the 3'UTR of the human LDL-receptor gene and their associations with plasma lipid levels in the Atherosclerosis Risk in Communities study. |
Publication Type | Journal Article |
Year of Publication | 2007 |
Authors | Muallem H, North KE, Kakoki M, Wojczynski MK, Li X, Grove M, Boerwinkle E, Wilhelmsen KC, Heiss G, Maeda N |
Journal | Hum Genet |
Volume | 121 |
Issue | 3-4 |
Pagination | 421-31 |
Date Published | 2007 May |
ISSN | 0340-6717 |
Keywords | 3' Untranslated Regions, Animals, Atherosclerosis, Embryonic Stem Cells, Female, Gene Expression, Genes, Reporter, Haplotypes, Humans, Lipoproteins, Male, Mice, Polymorphism, Single Nucleotide, Receptors, LDL, Risk, White People |
Abstract | The low-density lipoprotein receptor (LDLR) plays a pivotal role in cholesterol homeostasis. However, the role of genetic variations in the 3'UTR of the LDLR in relation to plasma cholesterol has been largely understudied. Six SNPs, G44243A, G44332A, C44506G, G44695A, C44857T and A44964G, within the 5' region of the 3'UTR fall into three common haplotypes, GGCGCA, AGCACG, and GGCGTA, occurring at frequencies of 0.45, 0.31 and 0.17, respectively, in Caucasians (n = 29) and 0.13, 0.13 and 0.38, respectively, in African Americans (n = 32), with three other haplotypes occurring at lesser frequencies. In a tissue culture based system, expression of a reporter gene carrying a 3'UTR that includes the 1 kb nucleotide sequences corresponding to the AGCACG or GGCGTA was 70 or 63%, respectively, of the same sequence with GGCGCA. Genotyping of two "haplotype tagging" SNPs, C44857T and A44964G, in the Atherosclerosis Risk in Communities (ARIC) study population showed that in Caucasians, but not in African Americans, the inferred TA haplotype had a significant LDL-cholesterol lowering effect. The adjusted LDL-cholesterol levels in the TA/TA diplotypes were lower by 6.10 mg/dl in men (P |
DOI | 10.1007/s00439-007-0327-1 |
Alternate Journal | Hum Genet |
PubMed ID | 17273844 |
Grant List | R37 HL042630 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States HL42630 / HL / NHLBI NIH HHS / United States |