title: Association of TNF-α gene variations with thoracic aortic dissection risk in a Chinese Han population.
abstract: BACKGROUND
  Chronic inflammation may be involved in pathogenesis of thoracic aortic dissection (TAD). Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that plays an important role in pathological TAD progression. In this study, we determined wether genetic variants of TNF-α were associated with TAD.
  
  
  METHODS
  Frequency distributions of TNF-α promoter polymorphisms (-1031C/T,-857C/T,-308G/A, and -238G/A) were determined by direct sequencing. TNF-α plasma levels were measured by enzyme-linked immunosorbent assay. Plasma levels of TNF-α mRNA in peripheral-blood mononuclear cells were analyzed by real-time quantitative polymerase chain reaction amplification.
  
  
  RESULTS
  We found the TNF-α promoter -857C/T polymorphism is associated with disease progression susceptibility in TAD patients. The CC homozygote of TAD patients had a significantly higher risk of TAD than did T allele carriers (P< 0.05). Plasma TNF-α concentrations were also significantly higher in TAD patients than control subjects (P<0.05), and CC genotype carriers showed increased TNF-α levels compared with T allele carriers (P<0.05). Moreover, peripheral-blood mononuclear cells carrying the CC genotype showed increased TNF-α mRNA levels compared with cells carrying the T allele.
  
  
  CONCLUSIONS
  The -857C/T polymorphism of TNF-α promoter plays a role in the genetic variation underlying susceptibility of individuals to TAD progression. The CC genotype is associated with increased TNF-α expression in TAD patients, and may be an independent predictive factor for TAD.
authors.affiliation: Department of Cardiology, Cardiovascular Research Institute, the General Hospital of Shenyang Military, Shenyang, Liaoning, China - wxiaozeng@163.com.
authors.forename: Xiao M
authors.initials: XM
authors.lastname: DU
authors.forename: Li W
authors.initials: LW
authors.lastname: Liu
authors.forename: Zhan K
authors.initials: ZK
authors.lastname: DU
authors.forename: Ruo X
authors.initials: RX
authors.lastname: Gu
authors.forename: Ya L
authors.initials: YL
authors.lastname: Han
authors.forename: Xiao Z
authors.initials: XZ
authors.lastname: Wang
mesh_terms: D000328:Adult; D000784:Aortic Dissection / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D017545:Aortic Aneurysm, Thoracic / Q000097:blood / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D002681:China / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D012307:Risk Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000235:genetics*
chemical_list: D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha