title: TNF-α -308 genotypes are associated with TNF-α and TGF-β₁ mRNA expression in blood leucocytes of humans.
abstract: OBJECTIVE
  Tumor necrosis factor α (TNF-α) influences the pathogenesis of lung-fibrosis and carcinogenesis in normal cells. Polymorphisms of this gene are suggested to be associated with susceptibility to lung-diseases. Additionally TNF-α is postulated to play a significant role in regulating. Transforming growth factor (TGF-β₁) expression Therefore we investigated if the TNF-α or TGF-β₁ gene expression level is different within the -308 TNF-α genotypes.
  
  
  METHODS
  Quantitative Real-time PCR of TNF-α and TGF-β₁ was performed in 178 Germans. Calculations of expression were made with the 2(-ΔΔCT) method. Detection of the -308 promoter polymorphism of the TNF-α gene was performed by rapid capillary PCR with melting curve analysis.
  
  
  RESULTS
  The relative TNF-α mRNA expression revealed significant differences between the TNF-α -308 homozygote wild-type G/G (0.00079±0.00011; n=113) and the heterozygote genotype G/A (0.0005±0.00008; n=52; p=0.030) as well as between homozygote wild-type G/G and the homozygote mutant A/A (0.00029±0.00009; n=5; p=0.004). The relative TGF-β mRNA expression showed, similar to TNF-α, the highest mRNA expression was seen within the TNF-α -308 homozygote wild-types, while the lowest mRNA expression lay within the homozygote mutant-types.
  
  
  CONCLUSIONS
  Our findings suggest that the G-allele of TNF-α -308 is associated with a significantly higher TNF-α mRNA expression compared to the A-allele and that this also reflects in TGF-β expression. Therefore we support the thesis that TGF-β is regulated by TNF-α.
authors.affiliation: Institut und Poliklinik für Arbeits- und Sozialmedizin, Justus-Liebig-Universität, Aulweg 129, D-35392 Giessen, Germany. Simone.Helmig@arbmed.med.uni-giessen.de
authors.forename: Simone
authors.initials: S
authors.lastname: Helmig
authors.forename: Nahid
authors.initials: N
authors.lastname: Aliahmadi
authors.forename: Peter
authors.initials: P
authors.lastname: Stephan
authors.forename: Juliane
authors.initials: J
authors.lastname: Döhrel
authors.forename: Joachim
authors.initials: J
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D005260:Female; D015870:Gene Expression; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D055815:Young Adult
chemical_list: D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; D014409:Tumor Necrosis Factor-alpha