Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Full Paper
  • Published:

The TNF−α –308, MCP−1 –2518 and TGF−β1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants

Genes & Immunity volume 4, pages 420–426 (2003)Cite this article

Abstract

Chronic lung disease (CLD) in premature newborns is associated with increased concentrations of inflammatory cytokines in tracheal aspirates (TA). We determined if polymorphisms of cytokine genes influence the risk of developing CLD by genotyping 178 mechanically ventilated very low birth weight (VLBW) infants for the tumor necrosis factor-α (TNF-α) −308 G/A, transforming growth factor-β1 (TGF-β1) +915 G/C and monocyte chemoattractant protein-1 (MCP-1) −2518 A/G polymorphisms. Genomic DNA was isolated from TA and genotypes determined by restriction length polymorphism. There was no effect of any of these polymorphisms on the development of CLD (29 vs 23%, P=0.371, TNF-α −308 AA/AG vs TNF-α −308 GG; 23 vs 26%, P=0.681, MCP-1 −2518 GG/AG vs MCP-1 −215-8 AA; 24 vs 24%, P=0.978, TGF-β1 +915 CG vs TGF-β1 +915 GG). TA IL-8 and MCP-1 concentrations were not different between genotype groups. Infants with the TNF-α −308 A allele had increased risk of IVH (RR 2.07; 95% CI 1.02–4.18, P=0.041) and infants with the TGF-β1 +915 C allele were at greater risk of death (32 vs 9%, P=0.016). These data suggest that these polymorphisms do not play a significant role in determining risk for CLD in preterm infants, but may play a role in other complications in the neonatal period.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Patterson AM, Taciak V, Lovchik J, Fox RE, Campbell AB, Viscardi RM . Ureaplasma urealyticum respiratory tract colonization is associated with an increase in interleukin 1-beta and tumor necrosis factor alpha relative to interleukin-6 in tracheal aspirates of preterm infants. Ped Infect Dis J 1998; 17: 321–328.

    Article  CAS  Google Scholar 

  2. Jonsson B, Tullus K, Brauner A, Lu Y, Noack G . Early increase of TNF and IL-6 in tracheobronchial aspirate fluid indicator of subsequent chronic lung disease in preterm infants. Arch Dis Child Fetal Neonatal Ed 1997; 77: F198–F201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kotecha S, Wilson L, Wangoo A, Silverman M, Shaw RJ . Increase in interleukin (IL)-1 beta and IL-6 in bronchoalveolar lavage fluid obtained from infants with chronic lung disease of prematurity. Pediatr Res 1996; 40: 250–256.

    Article  CAS  PubMed  Google Scholar 

  4. Kotecha S, Chan B, Azam N, Silverman M, Shaw RJ . Increase in interleukin-8 and soluble intercellular adhesion molecule-1 in bronchoalveolar lavage fluid from premature infants who develop chronic lung disease. Arch Dis Child Fetal Neonatal Ed 1995; 72: F90–F96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Munshi UK, Niu JO, Siddiq MM, Parton LA . Elevation of interleukin-8 and interleukin-6 precedes the influx of neutrophils in tracheal aspirates from preterm infants who develop bronchopulmonary dysplasia. Pediatr Pulmonol 1997; 24: 331–336.

    Article  CAS  PubMed  Google Scholar 

  6. Baier RJ, Loggins J, Kruger TE . Monocyte chemoattractant protein-1 and interleukin-8 are increased in bronchopulmonary dysplasia. Relation to isolation of Ureaplasma urealyticum. J Investig Med 2001; 49: 362–369.

    Article  CAS  PubMed  Google Scholar 

  7. Kotecha S, Wangoo A, Silverman M, Shaw RJ . Increase in the concentration of transforming growth factor beta-1 in bronchoalveolar lavage fluid before development of chronic lung disease of prematurity. J Pediatr 1996; 128: 464–469.

    Article  CAS  PubMed  Google Scholar 

  8. Jonsson B, Li YH, Noack G, Brauner A, Tullus K . Downregulatory cytokines in tracheobronchial aspirate fluid from infants with chronic lung disease of prematurity. Acta Paediatr 2000; 89: 1375–1380.

    Article  CAS  PubMed  Google Scholar 

  9. Wilson AG, di Giovine FS, Blakemore AIF, Duff GW . Single base polymorphism in the human tumour necrosis factor alpha gene detectable by NcoI restriction of PCR product. Hum Mol Genetics 1992; 1: 353.

    Article  CAS  Google Scholar 

  10. Braun N, Michel U, Ernst BP et al. Gene polymorphism at position −308 of the tumor-necrosis-factor-alpha (TNF-alpha) in multiple sclerosis and it's influence on the regulation of TNF-alpha production. Neurosci Lett 1996; 215: 75–78.

    CAS  PubMed  Google Scholar 

  11. Kroeger KM, Carville KS, Abraham LJ . The −308 tumor necrosis factor-alpha promoter polymorphism effects transcription. Mol Immunol 1997; 34: 391–399.

    Article  CAS  PubMed  Google Scholar 

  12. Louis E, Franchimont D, Piron A et al. Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin Exp Immunol 1998; 113: 401–406.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Moffatt MF, Cookson WO . Tumour necrosis factor haplotypes and asthma. Hum Mol Genet 1997; 6: 551–554.

    Article  CAS  PubMed  Google Scholar 

  14. Whyte M, Hubbard R, Meliconi R et al. Increased risk of fibrosing alveolitis associated with interleukin-1 receptor antagonist and tumor necrosis factor-alpha gene polymorphisms. Am J Respir Crit Care Med 2000; 162: 755–758.

    Article  CAS  PubMed  Google Scholar 

  15. Kim KA, Cho YY, Cho JS et al. Tumor necrosis factor-alpha gene promoter polymorphism in coal workers' pneumoconiosis. Mol Cell Biochem 2002; 234–235: 205–209.

    Article  PubMed  Google Scholar 

  16. Santana A, Saxena B, Noble NA, Gold LI, Marshall BC . Increased expression of transforming growth factor isoforms (β1, β2, β3) in bleomycin-induced pulmonary fibrosis. Am J Respir Cell Mol Biol 1995; 13: 34–44.

    Article  CAS  PubMed  Google Scholar 

  17. El-Gamel A, Awad MR, Sim E et al. Transforming growth factor-β1 and lung allograft fibrosis. Eur J Cardio-Thoracic Surg 1998; 13: 424–430.

    Article  CAS  Google Scholar 

  18. Awad MR, El-Gamel A, Hasleton P, Turner DM, Sinnott PJ, Hutchinson IV . Genotypic variation in the transforming growth factor-β1 gene. Association with transforming growth factor-β1 production, fibrotic lung disease, and graft fibrosis after lung transplantation. Transplant 1998; 66: 1014–1020.

    Article  CAS  Google Scholar 

  19. Arkwright DA, Laurie S, Super M et al. TGF-β1 genotype and accelerated decline in lung function of patients with cystic fibrosis. Thorax 2000; 55: 459–462.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Perrey C, Pravica V, Sinnott PJ, Hutchinson IV . Genotyping for polymorphisms in interferon-gamma, interleukin-10, transforming growth factor-beta 1 and tumor necrosis factor-alpha genes: a technical report. Transpl Immunol 1998; 6: 193–197.

    Article  CAS  PubMed  Google Scholar 

  21. Mukaida N, Harada A, Matsushima K . Interleukin-8 (IL-8) and monocyte chemotactic and activating factor (MCAF/MCP-1), chemokines essentially involved in inflammatory and immune reactions. Cytokine Growth Factor Rev 1998; 9: 9–23.

    Article  CAS  PubMed  Google Scholar 

  22. Vaillant P, Menard O, Vignaud JM, Martinet N, Martinet Y . The role of cytokines in human lung fibrosis. Monaldi Arch Chest Dis 1996; 51: 145–152.

    CAS  PubMed  Google Scholar 

  23. Smith RE, Strieter RM, Zhang K et al. A role for C–C chemokines in fibrotic lung disease. J Leukocyte Biol 1995; 57: 782–787.

    Article  CAS  PubMed  Google Scholar 

  24. Smith RE, Strieter RM, Phan SH, Kunkel SL . C–C chemokines: novel mediators of the profibrotic inflammatory response to bleomycin challenge. Am J Respir Cell Mol Biol 1996; 15: 693–702.

    Article  CAS  PubMed  Google Scholar 

  25. Car BD, Meloni F, Luisetti M, Semenzato G, Gialdroni-Grassi G, Walz A . Elevated IL-8 and MCP-1 in the bronchoalveolar lavage fluid of patients with idiopathic pulmonary fibrosis and pulmonary sarcoidosis. Am J Respir Crit Care Med 1994; 149: 655–659.

    Article  CAS  PubMed  Google Scholar 

  26. Rovin BH, Lu L, Saxena R . A novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem Biophys Res Commun 1999; 259: 344–348.

    Article  CAS  PubMed  Google Scholar 

  27. Szalai C, Kozma GT, Nagy A et al. Polymorphism in the gene regulatory region of MCP-1 is associated with asthma susceptibility and severity. J Allergy Clin Immunol 2001; 108: 375–381.

    Article  CAS  PubMed  Google Scholar 

  28. Watts CL, Bruce MC . Comparison of secretory component for immunoglobulin A with albumin as reference proteins in tracheal aspirate from preterm infants. J Pediatr 1995; 127: 113–122.

    Article  CAS  PubMed  Google Scholar 

  29. Reynard MP, Turner D, Navarrete CV . Allele frequencies of polymorphisms of the tumour necrosis factor-a, interleukin-10, interferon-gamma and interleukin-2 genes in a North European Caucasoid group from the UK. Eur J Immunogenet 2000; 27: 241–249.

    Article  CAS  PubMed  Google Scholar 

  30. Morse HR, Olomolaiye OO, Wood NAP, Keen LJ, Bidwell JL . Induced heterduplex genotyping of TNF-, IL-1β, IL-6 and IL-10 polymorphisms associated with transcriptional regulation. Cytokine 1999; 11: 789–795.

    Article  CAS  PubMed  Google Scholar 

  31. Hoffmann SC, St”anley EM, Cox ED et al. Ethnicity greatly influences cytokine gene polymorphism distribution. Am J Transplant 2002; 2: 560–567.

    Article  CAS  PubMed  Google Scholar 

  32. Conway DJ, Holland MJ, Bailey RL et al. Scarring trachoma is associated with polymorphism in the tumor necrosis factor alpha (TNF-alpha) gene promoter and with elevated TNF-alpha levels in tear fluid. Infect Immun 1997; 65: 1003–1006.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Aidoo M, McElroy PD, Kolczak MS et al. Tumor necrosis factor-alpha promoter variant 2 (TNF2) is associated with pre-term delivery, infant mortality, and malaria morbidity in western Kenya. Genet Epidemiol 2001; 21: 201–211.

    Article  CAS  PubMed  Google Scholar 

  34. Roberts AK, Monzon-Bordonaba F, Van Deerlin PG et al. Association of polymorphism within the promoter of the tumor necrosis factor alpha gene with increased risk of preterm premature rupture of the fetal membranes. Am J Obstet Gynecol 1999; 80: 1297–1302.

    Article  Google Scholar 

  35. Silverstein FS, Barks JD, Hagan P, Liu XH, Ivacko J, Szaflarski J . Cytokines and perinatal brain injury. Neurochem Int 1997; 30: 375–383.

    Article  CAS  PubMed  Google Scholar 

  36. Galasso JM, Wang P, Martin D, Silverstein FS . Inhibition of TNF-alpha can attenuate or exacerbate excitotoxic injury in neonatal rat brain. Neuroreport 2000; 11: 231–235.

    Article  CAS  PubMed  Google Scholar 

  37. Wood NA, Thomson SC, Smith RM, Bidwell JL . Identification of human TGF-beta1 signal (leader) sequence polymorphisms by PCR-RFLP. J Immunol Methods 2000; 234: 117–122.

    Article  CAS  PubMed  Google Scholar 

  38. Bancalari E, Abdenour GE, Feller R, Gannon J . Bronchopulmonary dysplasia: clinical presentation. J Pediatr 1979; 95: 819–823.

    Article  CAS  PubMed  Google Scholar 

  39. Shennan AT, Dunn MS, Ohlsson A, Lennox, Hoskins EM . Abnormal pulmonary outcomes in premature infants: prediction from oxygen requirement in the neonatal period. Pediatrics 1988; 82: 527–532.

    CAS  PubMed  Google Scholar 

  40. Palta M, Sadek M, Barnet JH et al. Evaluation of criteria for chronic lung disease in surviving very low birth weight infants. Newborn Lung Project. J Pediatr 1998; 132: 57–63.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the EP Stiles Award and the Department of Pediatrics LSUHSC.

Author information

Authors and Affiliations

  1. Department of Pediatrics, University of Mississippi Medical Center, Jackson, MS, USA

    K Adcock

  2. Department of Pediatrics, Louisiana State University Health Sciences Center, Shreveport, LA, USA

    C Hedberg, J Loggins, T E Kruger & R J Baier

Authors
  1. K Adcock
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Hedberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Loggins
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. T E Kruger
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. R J Baier
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to R J Baier.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Adcock, K., Hedberg, C., Loggins, J. et al. The TNF−α –308, MCP−1 –2518 and TGF−β1 +915 polymorphisms are not associated with the development of chronic lung disease in very low birth weight infants. Genes Immun 4, 420–426 (2003). https://doi.org/10.1038/sj.gene.6363986

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6363986

Keywords

This article is cited by

Search

Advanced search

Quick links