title: Genetic variation in liver X receptor alpha and risk of ischemic vascular disease in the general population.
abstract: OBJECTIVE
  Although animal studies indicate that liver X receptor alpha (LXRα) might influence risk of atherosclerosis, data in humans remain scarce. We tested the hypothesis that genetic variation in LXRα associates with risk of ischemic vascular disease and/or plasma lipid and lipoprotein levels in the general population.
  
  
  RESULTS
  We studied 10,281 white persons of Danish ancestry from a general population cohort, including 1,986 in whom ischemic heart disease (IHD) developed, and 989 in whom ischemic cerebrovascular disease developed. We examined another 51,429 white persons of Danish ancestry from a general population study, including 3,789 with IHD. We genotyped 10 genetic variants identified by resequencing LXRα. Homozygosity for -840AA/-115AA(=2.7%) predicted hazard ratios of 1.3 (95% confidence interval, 1.0-1.7) for IHD, 1.6 (1.2-2.2) for myocardial infarction, and 1.7 (1.3-2.4) for ischemic cerebrovascular disease. The corresponding odds ratios in the second cohort were 1.1 (0.9-1.4) for IHD and 1.5 (1.1-2.0) for myocardial infarction. In the combined studies, odds ratios were 1.2 (1.0-1.4) for IHD and 1.5 (1.2-1.9) for myocardial infarction. Homozygosity for -840AA/-115AA did not associate with lipid or lipoprotein levels. LXRα -1830T>C (tagging the haplotype -1830C/-840A/-115A, all r(2)≥0.97) associated with 91% increased transcriptional activity.
  
  
  CONCLUSIONS
  This study suggests that functional genetic variation in LXRα predicts risk of ischemic vascular disease in the general population.
authors: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
authors: Stefan
authors: S
authors: Stender
authors: Ruth
authors: R
authors: Frikke-Schmidt
authors: Aristomenis
authors: A
authors: Anestis
authors: Dimitris
authors: D
authors: Kardassis
authors: Amar A
authors: AA
authors: Sethi
authors: Børge G
authors: BG
authors: Nordestgaard
authors: Anne
authors: A
authors: Tybjærg-Hansen
mesh_terms: D000328:Adult; D000368:Aged; D002561:Cerebrovascular Disorders / Q000453:epidemiology* / Q000235:genetics; D003430:Cross-Sectional Studies; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D014644:Genetic Variation / Q000235:genetics*; D005838:Genotype; D006720:Homozygote; D006801:Humans; D000071518:Liver X Receptors; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology* / Q000235:genetics; D057093:Orphan Nuclear Receptors / Q000235:genetics*; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D012307:Risk Factors
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D057093:Orphan Nuclear Receptors