title: Association of combined genetic variations in PPARγ, PGC-1α, and LXRα with coronary artery disease and severity in Thai population.
abstract: BACKGROUND
  Atherosclerosis is a major cause of coronary artery disease (CAD). Peroxisome proliferator-activated receptor-γ (PPARγ), liver X receptor-α (LXRα), and PPARγ co-activator-1α (PGC-1α) are nuclear factors that regulate lipid metabolism and inflammation implicated in atherosclerosis. Although association of genetic variations in these nuclear factors with CAD risk has been reported, it was based on individual gene with inconsistent results among different ethnicities. We investigated the association of combined gene-polymorphisms of these nuclear factors with the risk and severity of CAD in Thai population.
  
  
  METHODS
  Hospital-based subjects, 225 CADs and 162 non-CADs, were genotyped for PPARγ C1431T, PGC-1α G482S, and LXRα -115G/A polymorphisms. Gene-polymorphisms were examined for their association with CAD risk and the severity of coronary atherosclerosis, assessed by both the number of main vessels with ≥50% stenosis and Gensini score.
  
  
  RESULTS
  The minor allele frequencies were 21.6% (1431T), 44.8% (482S), and 10.7% (-115A). Initially, only 482S allele revealed association with CAD risk [OR = 1.64 (95%CI: 1.01-2.66), P = 0.048] and severity [ORs for four-vessel disease = 1.23 (95%CI: 1.01-1.48), P = 0.036, and for severe atherosclerosis (score >32) = 1.76 (95%CI: 1.05-2.96), P = 0.032]. Combined two risk-genotypes, 1431T/482S and -115GG/482S, also predicted the risk of CAD [OR = 1.87 (95%CI: 1.09-3.21), P = 0.023 and OR = 1.87 (95%CI: 1.15-3.03), P = 0.012 respectively]. The combination of three risk-genotypes further increased the risk of both CAD [OR = 2.13 (95%CI: 1.12-4.06), P = 0.022] and severe coronary atherosclerosis [OR = 2.09 (95%CI 1.09-4.02), P = 0.027].
  
  
  CONCLUSIONS
  The combined PPARγ C1431T, PGC-1α G482S, and LXRα -115G/A polymorphisms increased the risk of CAD and predicted the severity of coronary atherosclerosis in Thais.
authors.affiliation: Biomedical Sciences Program, Graduate School, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Pratthana
authors.initials: P
authors.lastname: Yongsakulchai
authors.affiliation: Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand. Electronic address: schatr@kku.ac.th.
authors.forename: Chatri
authors.initials: C
authors.lastname: Settasatian
authors.affiliation: Department of Clinical Chemistry, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Nongnuch
authors.initials: N
authors.lastname: Settasatian
authors.affiliation: Department of Clinical Microscopy, Faculty of Associated Medical Sciences, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Nantarat
authors.initials: N
authors.lastname: Komanasin
authors.affiliation: Department of Physiology, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Upa
authors.initials: U
authors.lastname: Kukongwiriyapan
authors.affiliation: Department of Oncology, Wayne State University School of Medicine, Detroit, MI 48201, USA.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Cote
authors.affiliation: Queen Sirikit Heart Center of the Northeast, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Pongsak
authors.initials: P
authors.lastname: Intharapetch
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen 40002, Thailand; Queen Sirikit Heart Center of the Northeast, Khon Kaen University, Khon Kaen 40002, Thailand; Cardiovascular Research Group, Khon Kaen University, Khon Kaen 40002, Thailand.
authors.forename: Vichai
authors.initials: V
authors.lastname: Senthong
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D003251:Constriction, Pathologic / Q000235:genetics; D003324:Coronary Artery Disease / Q000208:ethnology / Q000235:genetics*; D003710:Demography; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D007249:Inflammation; D000071518:Liver X Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D047495:PPAR gamma / Q000235:genetics*; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D013785:Thailand
chemical_list: D000071518:Liver X Receptors; C000605213:NR1H3 protein, human; D047495:PPAR gamma; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
keywords: Atherosclerosis; Coronary artery disease; LXRα −115G/A; PGC-1α G482S; PPARγ C1431T; Severity of coronary atherosclerosis