TNF-α −308 genotypes are associated with TNF-α and TGF-β 1 mRNA expression in blood leucocytes of humans

Abstract

Aim 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-β 1) expression Therefore we investigated if the TNF-α or TGF-β 1 gene expression level is different within the −308 TNF-α genotypes. Methods Quantitative Real-time PCR of TNF-α and TGF-β 1 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. Conclusion 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.