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Genetic variation in lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) gene and the risk of coronary artery disease.

Abstract：

BACKGROUND:We examined the association of 3 polymorphisms in the lectin-like oxidized LDL receptor-1 (LOX1 or OLR1) gene with coronary artery disease in the Women's Ischemia Syndrome Evaluation (WISE) study population. METHODS AND RESULTS:The WISE sample comprised 589 white and 122 black women who underwent angiography for suspected ischemia. The sample was divided into 3 groups: <20% stenosis (38.7%), 20% to 49% stenosis (24.9%), and >or=50% stenosis (35.3%). The three LOX1 polymorphisms (intron 4/G-->A, intron 5/T-->G, and 3' UTR/T-->C) were in linkage disequilibrium and thus behaved as a single polymorphism. The frequency of the 3'UTR/T allele was significantly higher in whites than blacks (49% versus 19%; P<0.0001). Among white women, the frequency of the 3'UTR/T allele carriers (TC+TT genotypes) increased gradually from 67.9% to 75.0% and 79.2% in the <20%, 20% to 49%, and >or=50% stenosis groups, respectively (chi2 trend=6.23; P=0.013). Logistic regression analyses indicated that APOE (odds ratio, 1.90; P=0.007) and LOX1 (odds ratio, 1.67; P=0.025) genotypes were independently associated with the risk of disease and that there was no interaction between the two genes. The 3'UTR/T allele carriers also had significantly higher IgG anti-oxLDL levels than individuals carrying the CC genotype (0.94+/-0.20 versus 0.86+/-0.16; P=0.032). Furthermore, our electrophoretic mobility shift assay data show that the 3'UTR polymorphic sequence affects the binding of a putative transcription factor in an allele-specific manner. CONCLUSIONS:Our data suggest that common genetic variation in the LOX1 gene may be associated with the risk of coronary artery disease in white women.

journal_name

Circulation

journal_title

Circulation

authors

Chen Q,Reis SE,Kammerer C,Craig WY,LaPierre SE,Zimmer EL,McNamara DM,Pauly DF,Sharaf B,Holubkov R,Bairey Merz CN,Sopko G,Bontempo F,Kamboh MI

doi

10.1161/01.CIR.0000074207.85796.36

subject

Has Abstract

pub_date

2003-07-01 00:00:00

pages

3146-51

issue

eissn

0009-7322

issn

1524-4539

pii

01.CIR.0000074207.85796.36

journal_volume

107

pub_type

杂志文章,多中心研究

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Genetic variation in lectin-like oxidized low-density lipoprotein receptor 1 (LOX1) gene and the risk of coronary artery disease.