title: 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.
  
  
  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.
authors.affiliation: Department of Human Genetics, University of Pittsburgh, PA 15261, USA.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Steven E
authors.initials: SE
authors.lastname: Reis
authors.forename: Candace
authors.initials: C
authors.lastname: Kammerer
authors.forename: Wendy Y
authors.initials: WY
authors.lastname: Craig
authors.forename: Sue E
authors.initials: SE
authors.lastname: LaPierre
authors.forename: Erin Luedecking
authors.initials: EL
authors.lastname: Zimmer
authors.forename: Dennis M
authors.initials: DM
authors.lastname: McNamara
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Pauly
authors.forename: Barry
authors.initials: B
authors.lastname: Sharaf
authors.forename: Richard
authors.initials: R
authors.lastname: Holubkov
authors.forename: C Noel
authors.initials: CN
authors.lastname: Bairey Merz
authors.forename: George
authors.initials: G
authors.lastname: Sopko
authors.forename: Franklin
authors.initials: F
authors.lastname: Bontempo
authors.forename: M Ilyas
authors.initials: MI
authors.lastname: Kamboh
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000483:Alleles; D001057:Apolipoproteins E / Q000235:genetics; D001323:Autoantibodies / Q000097:blood; D044383:Black People / Q000235:genetics; D017023:Coronary Angiography; D003324:Coronary Artery Disease / Q000000981:diagnostic imaging / Q000235:genetics*; D024202:Electrophoretic Mobility Shift Assay; D005260:Female; D014644:Genetic Variation; D006579:Heterozygote; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007075:Immunoglobulin M / Q000097:blood; D007438:Introns / Q000235:genetics; D015810:Linkage Disequilibrium; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics; D011973:Receptors, LDL / Q000235:genetics*; D051131:Receptors, Oxidized LDL; D018570:Risk Assessment; D012307:Risk Factors; D051127:Scavenger Receptors, Class E; D044465:White People / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D001057:Apolipoproteins E; D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M; C495137:OLR1 protein, human; D012333:RNA, Messenger; D011973:Receptors, LDL; D051131:Receptors, Oxidized LDL; D051127:Scavenger Receptors, Class E