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.

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. Research Abstract Details 

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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. Abstract Text:

Hind Muallem,Kari E North,Masao Kakoki,Mary K Wojczynski,Xia Li,Megan Grove,Eric Boerwinkle,Kirk C Wilhelmsen,Gerardo Heiss,Nobuyo Maeda,

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 < 0.001) and by 4.63 mg/dl in women (P < 0.01) than in individuals with other diplotypes. Caucasian men homozygous for CA, in contrast, showed significantly higher LDL-cholesterol (P < 0.04), lower HDL-cholesterol (P < 0.02) and higher LDL/HDL ratios (P < 0.001). Thus our data shows that 3'UTR sequences that cause higher reporter gene expression in vitro are associated in Caucasians with plasma lipid profiles indicative of higher cardiovascular risk, suggesting that further studies of quantitative variants in the LDLR gene will be valuable.

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. Publishing Authors By Initials

H Muallem,KE North,M Kakoki,MK Wojczynski,X Li,M Grove,E Boerwinkle,KC Wilhelmsen,G Heiss,N Maeda,

For similar investigative techniques: epidemiologic methods: statistics as topic: probability: risk research abstracts see: investigative techniques: epidemiologic methods: statistics as topic: probability: risk research

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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. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Human genetics

VOLUME: 121

Page Numbers: 421-31

Journal Abbreviation:

ISSN: 0340-6717

DAY: 2

MONTH: 02

YEAR: 2007

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. Information

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LANGUAGE: eng

NlmUniqueID: 7613873

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. Keywords Mesh Terms:

KEYWORDS: Risk

MESH TERMS: genetics

Chemical & Substance for Abstract: 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. Information

Substance Name: Receptors, LDL

Registry Number: 0

Grant and Affiliation Information for 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.

AFFILIATION: Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599-7525, USA.

Country: Germany

AGENCY: United States NHLBI

GRANT: N01-HC-55022

ACRONYM: HC

MEDLINETA: Hum Genet

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