Abstract
The genes for tumor necrosis factor-α (TNF-α; TNF) and lymphotoxin-α (LT-α; LTA) are arranged in tandem within MHC III region of chromosome 6 in the same transcriptional orientation. This formation is conserved, even in marsupials, suggesting that there may be some functional advantage to this arrangement. The proteins encoded by TNF and LTA are known to interact as complementary factors in various cell signaling networks. Single nucleotide polymorphism sites for TNF (-308 G>A) and LTA (252 A>G) were investigated with TaqMan allelic discrimination assay. 190 cystic fibrosis (CF) subjects were enrolled into the study. The distribution of allelic variants of TNF and LTA genes in CF patients did not differ from those in health subjects of Moscow and European populations. We did not find any association between TNF genotypes and CF lung disease progression. In the same time the carriers of -308A allele more frequently had asthma and other atopic disorders as compared to patients homozygous for -308G allele (14.9 vs 5.3%, p<0.05). There was no case of tuberculosis among patients with 252G alleles. In the same time in 7.9% of 252A/A carriers tuberculosis infection was documented (p<0.03). Besides, the subjects with genotype 252A/A demonstrated a significant elevation of plasma TGF-β1 in comparison with carriers of 252G allele (72.6 vs 32.4 pg/ml; p<0.05). Our data confirm the critical importance of -308 A TNF allele for asthma development and provide robust evidence that LTA gene variants are involved in tuberculosis etiology.
- © 2011 ERS
