TNF-α-308 genotypes are associated with TNF-α and TGF-β1 mRNA expression in blood leucocytes of humans

Aim: Tumor necrosis factor alpha (TNF-alpha) 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-alpha is postulated to play a significant role in regulating. Transforming growth factor (TGF-beta(1)) expression Therefore we investigated if the TNF-alpha or TGF-beta(1) gene expression level is different within the -308 TNF-alpha genotypes. Methods: Quantitative Real-time PCR of TNF-alpha and TGF-beta(1) was performed in 178 Germans. Calculations of expression were made with the 2(-Delta Delta CT) method. Detection of the -308 promoter polymorphism of the TNF-alpha gene was performed by rapid capillary PCR with melting curve analysis. Results: The relative TNF-alpha mRNA expression revealed significant differences between the TNF-alpha -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-beta mRNA expression showed, similar to TNF-alpha, the highest mRNA expression was seen within the TNF-alpha -308 homozygote wild-types, while the lowest mRNA expression lay within the homozygote mutant-types. Conclusion: Our findings suggest that the G-allele of TNF-alpha -308 is associated with a significantly higher INF-alpha mRNA expression compared to the A-allele and that this also reflects in TGF-beta expression. Therefore we support the thesis that TGF-beta is regulated by TNF-alpha. 2010 Elsevier Ltd. All rights reserved.