Tumor necrosis factor-α gene promoter polymorphism in coal workers’ pneumoconiosis

  • Kyoung Ah Kim
  • Yong-Yeun Cho
  • Jung Sik Cho
  • Ki Hwa Yang
  • Woon Kyu Lee
  • Kweon-Haeng Lee
  • Yun Shin Kim
  • Young Liml
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)


Tumor necrosis factor-alpha (TNF-a) is believed to play a central role in the pathogenesis of pneumoconiosis. TNF2, a polymorphism in the TNF-a gene promoter, has been associated with an increase in TNF-a production and airway inflammation. To investigate the frequency of TNF2 in patients who have coal workers’ pneumoconiosis (CWP) and to determine whether it is associated with development of a large opacity in CWP, we investigated the expression of the TNF2 allele in 80 patients who had CWP and in 54 healthy controls using restriction fragment length polymorphism (RFLP). Compared to controls (10.2%), the frequency of the TNF2 allele was greater in the CWP patients (20.6%). Furthermore, the TNF2 allele was very common in patients who had a large opacity (28.2%) in comparison with 13.4% in those with simple CWP. From these data, we suggest that the TNF2 allele is associated with the development of a large opacity in CWP. (Mol Cell Biochem 234/235: 205–209, 2002)

Key words

pneumoconiosis CWP tumor necrosis factor alpha promoter opacity TNF2 


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  1. 1.
    Borm PJ, Palmen N, Engelen JJ, Buurman WA: Spontaneous and stimulated release of tumor necrosis factor-a (TNF) from blood monocytes of miners with coal workers’ pneumoconiosis. Am Rev Respir Dis 138: 1589–1594, 1988PubMedGoogle Scholar
  2. 2.
    Lassalle P, Gosset P, Aerts C, Fournier E, Lafitte JJ, Degreef JM, Wallaert B, TonnelAB, Voisin C: Abnormal secretion of interleukin-1 and tumor necrosis factor-a by alveolar macrophages in coal workers’ pneumoconiosis: Comparison between simple pneumoconiosis and progressive massive fibrosis. Exp Lung Res 16: 73–80, 1990PubMedCrossRefGoogle Scholar
  3. 3.
    Schins RP, Borm PJ: Epidemiological evaluation release of monocyte TNF-a as an exposure and effect marker in pneumoconiosis: A five year follow up study among coal workers. Occup Environ Med 52: 441–450, 1995PubMedCrossRefGoogle Scholar
  4. 4.
    Driscoll KE: TNF alpha and MIP-2: Role in particle-induced inflammation and regulation by oxidative stress. Toxicol Lett 112–113: 177–183, 2000Google Scholar
  5. 5.
    Rink L, Kirchner H: Recent progress in the tumor necrosis factor-a field. Int Arch Aller Immunol I11: 199–209, 1996CrossRefGoogle Scholar
  6. 6.
    Probert L, Selmaj K: TNF and related molecules: Trends in neuroscience and clinical applications. J Neuroimmunol 72: 113–117, 1997PubMedCrossRefGoogle Scholar
  7. 7.
    Czaja AJ, Cookson S, Contantini PK, Clare M, Underhill JA, Donaldson PT: Cytokine polymorphisms associated with clinical features and treatment outcome in type 1 autoimmune hepatitis. Gastroenterology 117: 728–731, 1999CrossRefGoogle Scholar
  8. 8.
    Wilson AG, de Vries N, Pociot F, di Giovine FS, van der Putte LB, Duff GW: An allelic polymorphism within the human tumor necrosis factor-a promoter region is strongly associated with HLAA1, B8, and DR3 alleles. J Exp Med 177: 557–560, 1993PubMedCrossRefGoogle Scholar
  9. 9.
    Wilson AG, Symons JA, McDowell TL, McDewitt HO, Duff GW: Effects of a polymorphism in the human tumor necrosis factor a promoter on transcriptional activation. Proc Natl Acad Sci USA 94: 3195–3199, 1997PubMedCrossRefGoogle Scholar
  10. 10.
    Kroeger KM, Carville KS, Abraham LJ: The —308 tumor necrosis factor-a promoter polymorphism effects transcription. Mol Immunol 34: 391–399, 1997PubMedCrossRefGoogle Scholar
  11. 11.
    McGuire W, Hill AV, Allsopp CE, Greenwood BM, Kwiatkowski D: Variation in the TNF-a promoter region associated with susceptibility to cerebral malaria. Nature 371: 508–510, 1994PubMedCrossRefGoogle Scholar
  12. 12.
    Mira JP, Cariou A, Crall F, Declaux C, Losser MR, Hechmati F, Cheval C, Monchi M, Teboul JL, Riche F, Leleu G, Arbibe L, Mignon A, Delpech M, Dhainaut JF: Association of TNF2, a TNF-a promoter polymorphism, with septic shock susceptibility and mortality: A multicancer study. JAMA 282: 561–568, 1999PubMedCrossRefGoogle Scholar
  13. 13.
    Huang SL, Su CH, Chang SC: Tumor necrosis factor-alpha gene polymorphism in chronic bronchitis. Am J Respir Crit Care Med 156: 1436–1439, 1997Google Scholar
  14. 14.
    Li Kam Wa TC, Mansur AH, Britton J, Williams G, Pavord I, Richards K, Campbell DA, Morton N, Holgate ST, Morrison JF: Association between-308 tumor necrosis factor promoter polymorphism and bronchial hyperreactivity in asthma. Clin Exp Aller 29: 1204–1208, 1999CrossRefGoogle Scholar
  15. 15.
    Zhai R, Jetten M, Schins RP, Franssen H, Borm PJ: Polymorphism in the promoter of the tumor necrosis factor-alpha gene in coal miners. Am J Ind Med 34: 318–324, 1998PubMedCrossRefGoogle Scholar
  16. 16.
    Yucesoy B, Vallyathan V, Landsittel DP, Sharp DS, Weston A, Burleson GR, Simeonova P, McKinstry M, Luster MI: Association of tumor necrosis factor-and interleukin-1 gene polymorphisms with silicosis. Toxicol Appl Pharmacol 172: 75–82, 2001PubMedCrossRefGoogle Scholar
  17. 17.
    Parker JE, Banks DE: Lung disease in coal workers. In: D.E. Banks, J.E. Parker (eds). Occupational Lung Disease. An International Perspective. Chapman and Hall, London, 1998, pp 161–181Google Scholar
  18. 18.
    International Labour Office: Guidelines for the Use of ILO International Classification of Radiographs of Pneumoconioses. Revised Edition 1980, International Labour Office, Geneva, 1980, pp 1–20Google Scholar
  19. 19.
    Kim KA, Lim Y, Kim JH, Kim EK, Chang HS, Park YM, Ahn BY: Potential biomarker of coal workers’ pneumoconiosis. Toxicol Lett 108: 297–302, 1999PubMedCrossRefGoogle Scholar
  20. 20.
    Mycko M, Kowalski W, Kwinkowski M, Buenafe AC, Szymanska B, Tronczynska E, Plucienniczak A, Selmaj K: Multiple sclerosis: The frequency of allelic forms of tumor necrosis factor and lymphotoxin alpha. J Neuroimmunol 84: 198–206, 1998PubMedCrossRefGoogle Scholar
  21. 21.
    Jacob CO, Fronek Z, Lewis GD, Koo M, Hansen JA, McDevitt HO: Heritable major histocompatibility complex class II-associated differences in production of tumor necrosis factor-a: Relevance to genetic predisposition to systemic lupus erythematosus. Proc Natl Acad Sci USA 87: 1233–1237, 1990PubMedCrossRefGoogle Scholar
  22. 22.
    Pociot F, Briant L, Jongeneel CV, Molvig J, Worsaae H, Abbal M, Thomsen M, Nerup J, Cambon-Tompsen A: Association of tumor necrosis factor (TNF) and class II major histocompatibility complex alleles with the secretion ofTNF-a and TNF-I3 by human mononuclear cells: A possible link to insulin-dependent diabetes mellitus. Eur J Immunol 23: 224–231, 1993PubMedCrossRefGoogle Scholar
  23. 23.
    Kroeger KM, Abraham LJ: Identification of an AP-2 element in the —323 to —285 region of the TNF-alpha gene. Biochem Mol Biol Int 40: 43–51, 1996PubMedGoogle Scholar
  24. 24.
    Messer G, Kick G, Ranki A, Koskimies S, Reunala T, Meurer M: Polymorphism of the tumor necrosis genes in patients with dermatitis herpetiformis. Dermatology 189(suppl 1): 135–137, 1994PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Kyoung Ah Kim
    • 1
  • Yong-Yeun Cho
    • 2
  • Jung Sik Cho
    • 2
  • Ki Hwa Yang
    • 2
  • Woon Kyu Lee
    • 3
  • Kweon-Haeng Lee
    • 3
  • Yun Shin Kim
    • 4
  • Young Liml
    • 1
  1. 1.Department of Occupational and Environmental MedicineSt. Mary’s Hospital, The Catholic University of KoreaSeoulKorea
  2. 2.Department of General ToxicologyKorea Institute of Toxicological Research, Korea Food and Drug AdministrationSeoulKorea
  3. 3.Department of PharmacologyCollege of Medicine, The Catholic University of Korea;SeoulKorea
  4. 4.Department of Industrial MedicineCollege of Medicine, Hanyang UniversitySeoulKorea

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