title: Association between the ABCA1-565C/T gene promoter polymorphism and coronary heart disease severity and cholesterol efflux in the Chinese Han population.
abstract: BACKGROUND
  ABCA1 -565C/T gene promoter variants have been associated with the severity of coronary artery disease in Western populations. The purpose of our study was to investigate the association between the -565C/T gene polymorphism and coronary artery disease severity and cholesterol efflux in the Chinese Han population.
  
  
  METHODS
  A cohort of 298 acute coronary syndrome (ACS) patients and 541 healthy controls was genotyped using the highly sensitive ligase detection reaction. ABCA1 -565C/T genotype was correlated with the clinical features of 164 acute myocardial infarction (AMI) patients. Monocytes from patients with various -565C/T gene polymorphisms were isolated and differentiated into foam cells by coincubation with [(3)H]-labeled acetyl-low-density lipoprotein cholesterol. ABCA1 mRNA and protein expression levels were evaluated, as well as cellular cholesterol efflux.
  
  
  RESULTS
  The frequency of the TT genotype in the -565C/T polymorphism of ACS patients was significantly increased when compared with controls (0.211 vs. 0.162, p<0.05). The TT genotype, but not the CT or CC genotypes, in the -565C/T gene polymorphism correlated with the severity of the coronary lesion observed in AMI patients. Patients with the TT homozygote genotype also exhibited significantly lower cellular cholesterol efflux (TT [6.37%±0.554%]) levels than controls and also had the lowest levels of ABCA1 mRNA and protein expression among the group of variants. In contrast, cholesterol efflux levels in AMI patients with CT [11.35%±3.975%] and CC ([15.32%±6.293%]) genotypes were not significantly different from controls.
  
  
  CONCLUSIONS
  Impaired ABCA1-mediated cholesterol efflux in macrophages may be associated with the severity of the coronary lesions in AMI patients with the TT genotype at the -565C/T gene polymorphism.
authors.affiliation: 1 Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College , Chinese Academy of Medicine Science, Beijing, China .|2 Department of Second Geriatric Cardiology, The People's Liberation Army General Hospital , Beijing, China .
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Qi
authors.affiliation: 1 Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College , Chinese Academy of Medicine Science, Beijing, China .
authors.forename: Lian-Feng
authors.initials: LF
authors.lastname: Chen
authors.affiliation: 3 Department of Cardiology, FuWai Cardiovascular Disease Hospital, Peking Union Medical College , Chinese Academy of Medicine Science, Beijing, China .
authors.forename: Ai-Min
authors.initials: AM
authors.lastname: Dang
authors.affiliation: 1 Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College , Chinese Academy of Medicine Science, Beijing, China .
authors.forename: Li-Yun
authors.initials: LY
authors.lastname: Li
authors.affiliation: 1 Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College , Chinese Academy of Medicine Science, Beijing, China .
authors.forename: Quan
authors.initials: Q
authors.lastname: Fang
authors.affiliation: 1 Department of Cardiology, Peking Union Medical College Hospital, Peking Union Medical College , Chinese Academy of Medicine Science, Beijing, China .
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Yan
mesh_terms: D064286:ATP Binding Cassette Transporter 1 / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics*; D000368:Aged; D016022:Case-Control Studies; D002681:China; D002784:Cholesterol / Q000097:blood*; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D005820:Genetic Testing; D006801:Humans; D008264:Macrophages / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D061251:Primary Cell Culture; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
chemical_list: C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D012333:RNA, Messenger; D002784:Cholesterol