Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Jan 23:11:19.
doi: 10.1186/1479-5876-11-19.

TNF gene polymorphisms in cystic fibrosis patients: contribution to the disease progression

Galina Shmarina  1 , Alexander Pukhalsky, Nika Petrova, Ekaterina Zakharova, Lucine Avakian, Nikolai Kapranov, Vladimir Alioshkin
Affiliations

TNF gene polymorphisms in cystic fibrosis patients: contribution to the disease progression

Galina Shmarina et al. J Transl Med. .

Abstract

Background: It is well known that the disease progression in cystic fibrosis (CF) patients may be diverse in subjects with identical mutation in CFTR gene. It is quite possible that such heterogeneity is associated with TNF-α and/or LT-α gene polymorphisms since their products play a key role in inflammation. The aim of the study was to investigate the possible roles of TNF gene polymorphisms in CF disease phenotype and progression.

Methods: 198 CF patients and 130 control subjects were genotyped for both TNF-α-308GA and LT-α + 252AG polymorphisms.

Results: The carriers of the TNF-α-308A allele more frequently had asthma as compared to patients homozygous for the TNF-α-308 G allele. In 9 of 108 (8.3%) of LTα + 252AA carriers, tuberculosis infection has been documented, whereas there was no case of tuberculosis among patients, either homozygous or heterozygous for LTα +252 G alleles (p = 0.01). We never observed virus hepatitis among LTα + 252GA carriers. The genotypes TNF-α-308GG - LT-α + 252AA and TNF-α-308GA - LT-α + 252AG were unfavorable with regard to liver disease development (both p < 0.05). It was also shown that neutrophil elastase activity was higher in sputum specimens from high TNF producers with genotypes TNF-α-308GA or LT-α + 252GG. In addition the carriers of such genotypes demonstrated a higher risk of osteoporosis development (p values were 0.011 and 0.017, respectively).

Conclusions: The carriers of genotypes, which are associated with higher TNF-α production, demonstrated increased frequency of asthma, higher levels of neutrophil elastase, and decrease of bone density. On the contrary, the carriers of genotypes associated with low TNF-α production showed a higher frequency of tuberculosis infection.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Sputum elastase levels in carriers of different TNF-α -308 and LT-α +252 genotypes among cystic fibrosis patients.
Figure 2
Figure 2
Frequency of the bone mineral density decrease in carriers of different TNF-α -308 and LT-α +252 genotypes among cystic fibrosis patients.
See this image and copyright information in PMC

References

    1. Xie T, Rowen L, Aguado B, Ahearn ME, Madan A, Qin S, Campbell RD, Hood L. Analysis of the gene-dense major histocompatibility complex class III region and its comparison to mouse. Genome Res. 2003;13:2621–2636. doi: 10.1101/gr.1736803. - DOI - PMC - PubMed
    1. Campbell RD, Trowsdale J. Map of the human MHC. Immunol Today. 1993;14:349–352. doi: 10.1016/0167-5699(93)90234-C. - DOI - PubMed
    1. Bozzoni F, Beutler B. The tumor necrosis factor ligand and receptor families. N Engl J Med. 1996;334:1717–1725. doi: 10.1056/NEJM199606273342607. - DOI - PubMed
    1. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor superfamilies: integrating mammalian biology. Cell. 2001;104:487–501. doi: 10.1016/S0092-8674(01)00237-9. - DOI - PubMed
    1. Elewaut D, Ware CF. The unconventional role of LT alpha beta in T cell differentiation. Trends Immunol. 2007;28:169–175. doi: 10.1016/j.it.2007.02.005. - DOI - PubMed

Publication types