DOI xxxxxxxx

Gorovenko N.G.2, Zhurakhivska IM.V.1-2, Basanets A.V.1, Podolska S.V.2

GENETIC POLYMORPHISM OF TNF-a-30B*G/A. AS A BIOMARKER OF PNEUMOCONIOSIS RISK DEVELOPMENT IN COAL MINERS

1Institute for Occupational Health of AMS of Ukraine, Kiev

2National Medical Academy for Post-Graduate Education named after P.L Shupyk of MH of Ukraine, Kyiv

Full article (PDF), UKR

Coal Workers Pneumoconiosis (CWP) is one of the most widespread multifactorial diseases in occupational pathology. It requires new approaches to prophylaxis and studying the mechanisms of pathogenesis. Determination of inherited predispo-sition biomarkers to CWP can allow to define a risk group among workers and to provide them with the necessary medical care. One of possible biomarkers of inherited predisposition to CWP development is a gene tumor necrosis factor alpha (TNF- a-308*G/A) polymorphism.TNF-a alleles polymorphism was studied in 138 healthy subjects (control group) and 112 CWP patients with minimum 10 years of underground work experience. The presence of alleles was analyzed by PCR method and restriction fragment-length polymorphism (RFLP).The frequency of TNF-a-308*A allele in the control group was 8 %, and in the group of CWP patients — 11,6 %. The value of OR=l,5 (Cl: 0,8—2,76) specified the increase of risk of CWP development for carriers of the allele A. The frequency of G allele in healthy miners was not “significantly different from patients with CWP. The significant differences of frequencies in TNF-a genotypes in the controls and in the CWP patients groups were obtained only for TNF-a-308*G/A (OR =1,4, Cl: 0,8-2,7).The results indicate that the presence of the TNF-a-308*A allele and the TNF-a-308*G/A genotype can be a risk factor for development of CWP in Ukrainian coal miners.

Key words: biomarker, cool worker pneumoconiosis, timor necrosis factor

References

  1. Babich P.N.. Lapach S.N.. ChubenkoA.V. Primeneniye sovremennykh statisticheskikh metodov v praktike klinicheskikh issledovaniy. Soobshcheniye vtoroye. Primeneniye kriteriya khi-kvadrat//Ukr. med. chasopis.-2003,-No 2-S. 138-144.
  2. Gorovenko N.G., Basanets A.V., Zhurakhovskaya N.V. (2005), “Genetic studies in occupational pathology”, Zhurnal AMN Ukrainy, 11 (2), 346-360.
  3. Brinkman В.М., Huizinga T.W., Breedveld F.C., Verweij C.L. Allele-specific quantification of TNF transcripts in rheumatoid arthritis//Hum. Genet.- 1996.- No 97,-P. 813-818.
  4. D’Alfonso S.. Richiardi P.M. An intragenic polymorphism in the human tumor necrosis factor alpha (TNFa) chain-encoding gene//Immunogenetics.- 1996.- No 44.- P. 321-322.
  5. Hamann A., Mantzoros C.. Vldal-Puig A.. Flier J.S. Genetic variability in the TNF-alpha promoter is not associated with type II diabetes mellitus (NIDDM)// Biochem. Biophys. Res. Commun.- 1995.- No 211.-P. 833-839.
  6. Kim K.A., Lim Y.. Kim J.H. et al. Potential biomarker of coal workers' pneumoconiosis//Toxlcol. Lett.- 1999,- No 108.- P. 297-302.
  7. Kim K.A., Cho Y.Y.. Cho J.S. et al. Tumor necrosis factor-alpha gene promoter polymorphism in coal workers' pneumoconiosis//Mol. Cell Biochem.- 2002,- V.234-235. No 1-2 - P. 205-209.
  8. Kroeger K.. Carville K., Abraham L. The -308 Tumor Necrosis Factor-a promotor polymorphism effects transcription//Mol. Immunol.- 1997.-No 34,- P. 391-399.
  9. Moffatt M.F.. Cookson W. Tumour necrosis factor haplo-types and asthma//Hum. Mol. Gen.- 1997,-No 6,- P. 551-554.
  10. Nadif R.. Jedlicka A.. Mintz M.etal. Effect of TNF and LTA polymorphisms on biological markers of response to oxidative stimuli in coal miners: a model of gene-environment interaction.Tumour necrosis factor and lymphotoxin alpha//J. Med.Genet-2003,-V.40.No 2,-P.96-103.
  11. Nuntayanuwat S.. Dharakul T., Chaowagul W., Songsivilal S. Polymorphism in the promoter region of tumor necrosis factor-alpha gene is associated with severe mieloidosis//Hum. Immunol.- 1999.-No 60.-P. 979-983.
  12. Porcher J.M.. Oberson D.. Viseux N. et al. Evaluation of tumor necrosis factor-alpha (TNF) as an exposure or risk marker in three French coal mining regions//Exp. Lung Res.- 1994,-V.20. No 5.- P. 433-443.
  13. Schins R.P., Borm P.J. Plasma levels of soluble tumor necrosis factor receptors are increased in coal miners with pneumoconiosis//Eur. Respir. J. - 1995.- V.8. No 10.-P. 1658-1663.
  14. Vanhee D., Molet S.. Gosset P. et al. Expression of leukocyte-endothelial adhesion molecules is limited to intercellular adhesion molecule-1 (ICAM-1) in the lung of pneumoconiotic patients: role of tumour necrosis factor-alpha (TNF-alpha)//Clin. Exp. Immunol.- 1996.- V.106, No 3.-P. 541-548.
  15. Wilson A.G.. Symons J.A., McDowell T.L. et al. Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation//Proc. Natl. Acad. Sci. USA.- 1997.- No 94.- P. 3195-3199.
  16. Yucesoy B., Vallyathan V.. Landsittel D.P. et al. Cytokine polymorphisms in silicosis and other pneumoconioses//Mol. Cell Blochem.- 2002.- V.234-235, No 1-2,-P.219- 224.
  17. Yucesoy B., Van Vallyathan. Douglas P. et al. Association of Tumor Necrosis Factor-a and Interleukin- 1 Gene Polymorphisms with Silicosis//Toxicol. Appl. Pharmacol.- 2001.- No 173.- P. 75-82.
  18. Zhai R.. Jetten M.. Schins R.P.F. e al. Polymorphisms in promoter of the tumor necrosis factor gene in coal miners//Am. J. Ind. Med.- 1998.- No 34,-P. 318-324.
  19. Zhai R.. Liu G.. Ge X. et al. Serum levels of tumor necrosis factor-alpha (TNF-alpha). interleukin 6 (1L-6). and their soluble receptors in coal workers' pneumoconiosis//Respir. Med.-2002,-V.96, No 10,-P. 829-34.