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.

  • Short Communication
  • Published:

Genomic variations within DEFB1 are associated with the susceptibility to and the fatal outcome of severe sepsis in Chinese Han population

Genes & Immunity volume 8, pages 439–443 (2007)Cite this article

Abstract

Sepsis is a systemic inflammatory response syndrome to infection. Human β-defensin 1 (DEFB1) is a multifunctional mediator in infection and inflammation, which has been largely explored in ex vivo studies. The present case–control study was designed to investigate whether DEFB1 genomic variations are associated with the susceptibility to and the outcome of severe sepsis in 211 patients with severe sepsis and 157 ethnic-matched healthy controls. After correcting for multiple testing, the −44G/C was the only polymorphism found to show significant associations with both the susceptibility to and the fatal outcome of severe sepsis (P=0.0049, odd ratio (OR) 1.971 and P=0.002, OR 2.406, respectively). Haplotype −20A/−44C/−52G showed a protective role against severe sepsis (P=0.0066, OR 0.6751), whereas haplotype −20G/−44G/−52G served as a risk factor for the fatal outcome of severe sepsis (P=0.0052, OR 2.427). These findings provide further evidence that β-defensin 1 may play a role in the pathogenesis of severe sepsis.

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. Cohen J . The immunopathogenesis of sepsis. Nature 2002; 420: 885–891.

    Article  CAS  Google Scholar 

  2. Hotchkiss RS, Karl IE . The pathophysiology and treatment of sepsis. N Engl J Med 2003; 348: 138–150.

    Article  CAS  Google Scholar 

  3. Lin MT, Albertson TE . Genomic polymorphisms in sepsis. Crit Care Med 2004; 32: 569–579.

    Article  CAS  Google Scholar 

  4. Cobb JP, O'Keefe GE . Injury research in the genomic era. Lancet 2004; 363: 2076–2083.

    Article  CAS  Google Scholar 

  5. Yang D, Biragyn A, Hoover DM, Lubkowski J, Oppenheim JJ . Multiple roles of antimicrobial defensins, cathelicidins, and eosinophil-derived neurotoxin in host defense. Annu Rev Immunol 2004; 22: 181–215.

    Article  Google Scholar 

  6. Ganz T . Defensins: antimicrodial peptides of innate immunity. Nat Rev Immunol 2003; 3: 710–720.

    Article  CAS  Google Scholar 

  7. Bensch KW, Raida M, Magert HJ, Schulz-Knappe P, Forssmann WG . hBD-1: a novel β-defensin from human plasma. FEBS Lett 1995; 368: 331–335.

    Article  CAS  Google Scholar 

  8. Goldman MJ, Anderson GM, Stolzenberg ED, Kari UP, Zasloff M, Wilson JM . Human beta-defensin-1 is a salt-sensitive antibiotic in lung that is inactivated in cystic fibrosis. Cell 1997; 88: 553–560.

    Article  CAS  Google Scholar 

  9. Valore EV, Park CH, Quayle AJ, Wiles KR, McCray Jr PB, Ganz T . Human beta-defensin-1: an antimicrobial peptide of urogenital tissues. J Clin Invest 1998; 101: 1633–1642.

    Article  CAS  Google Scholar 

  10. Fang XM, Shu Q, Chen QX, Book M, Sahl HG, Hoeft A et al. Differential expression of alpha- and beta-defensins in human peripheral blood. Eur J Clin Invest 2003; 33: 82–87.

    Article  CAS  Google Scholar 

  11. Joly S, Organ CC, Johnson GK, McCray Jr PB, Guthmiller JM . Correlation between beta-defensin expression and induction profiles in gingival keratinocytes. Mol Immunol 2005; 42: 1073–1084.

    Article  CAS  Google Scholar 

  12. Sherman H, Chapnik N, Froy O . Albumin and amino acids upregulate the expression of human beta-defensin 1. Mol Immunol 2005; 43: 1617–1623.

    Article  Google Scholar 

  13. Schaller-Bals S, Schulze A, Bals R . Increased levels of antimicrobial peptides in tracheal aspirates of newborn infants during infection. Am J Respir Crit Care Med 2002; 165: 992–995.

    Article  Google Scholar 

  14. Hiratsuka T, Nakazato M, Ihi T, Minematsu T, Chino N, Nakanishi T et al. Structural analysis of human beta-defensin-1 and its significance in urinary tract infection. Nephron 2000; 85: 34–40.

    Article  CAS  Google Scholar 

  15. Dommisch H, Acil Y, Dunsche A, Winter J, Jepsen S . Differential gene expression of human beta-defensins (hBD-1, -2, -3) in inflammatory gingival diseases. Oral Microbiol Immunol 2005; 20: 186–190.

    Article  CAS  Google Scholar 

  16. Yang D, Chertov O, Bykovskaia SN, Chen Q, Buffo MJ, Shogan J et al. β-defensins: linking innate and adaptive immunity through dendritic and T cell CCR6. Science 1999; 286: 525–528.

    Article  CAS  Google Scholar 

  17. Sun L, Finnegan CM, Kish-Catalone T, Blumenthal R, Garzino-Demo P, La Terra Maggiore GM et al. Human β-defensins suppress human immunodeficiency virus infection: potential role in mucosal protection. J Virol 2005; 79: 14318–14329.

    Article  CAS  Google Scholar 

  18. Wehkamp J, Harder J, Weichenthal M, Mueller O, Herrlinger KR, Fellermann K et al. Inducible and constitutive beta-defensins are differentially expressed in Crohn's disease and ulcerative colitis. Inflamm Bowel Dis 2003; 9: 215–223.

    Article  Google Scholar 

  19. Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M et al. DNA sequence and analysis of human chromosome 8. Nature 2006; 439: 331–335.

    Article  CAS  Google Scholar 

  20. Hollox EJ, Armour JA, Barber JC . Extensive normal copy number variation of a beta-defensin antimicrobial-gene cluster. Am J Hum Genet 2003; 73: 591–600.

    Article  CAS  Google Scholar 

  21. Aldred PM, Hollox EJ, Armour JA . Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3. Hum Mol Genet 2005; 14: 2045–2052.

    Article  CAS  Google Scholar 

  22. Chen Q, Book M, Fang X, Hoeft A, Stuber F . Screening of copy number polymorphisms in human beta-defensin genes using modified real-time quantitative PCR. J Immunol Methods 2006; 308: 231–240.

    Article  CAS  Google Scholar 

  23. Linzmeier RM, Ganz T . Copy number polymorphisms are not a common feature of innate immune genes. Genomics 2006; 88: 122–126.

    Article  CAS  Google Scholar 

  24. Braida L, Boniotto M, Pontillo A, Tovo PA, Amoroso A, Crovella S . A single-nucleotide polymorphism in the human beta-defensin 1 gene is associated with HIV-1 infection in Italian children. AIDS 2004; 18: 1598–1600.

    Article  Google Scholar 

  25. Leung TF, Li CY, Liu EK, Tang NL, Chan IH, Yung E et al. Asthma and atopy are associated with DEFB1 polymorphisms in Chinese children. Genes Immun 2006; 7: 59–64.

    Article  CAS  Google Scholar 

  26. Levy H, Raby BA, Lake S, Tantisira KG, Kwiatkowski D, Lazarus R et al. Association of defensin beta-1 gene polymorphisms with asthma. J Allergy Clin Immunol 2005; 115: 252–258.

    Article  CAS  Google Scholar 

  27. Matsushita I, Hasegawa K, Nakata K, Yasuda K, Tokunaga K, Keicho N . Genetic variants of human beta-defensin-1 and chronic obstructive pulmonary disease. Biochem Biophys Res Commun 2002; 291: 17–22.

    Article  CAS  Google Scholar 

  28. Jurevic RJ, Bai M, Chadwick RB, White TC, Dale BA . Single-nucleotide polymorphisms (SNPs) in human beta-defensin 1: high-throughput SNP assays and association with Candida carriage in type I diabetics and nondiabetic controls. J Clin Microbiol 2003; 41: 90–96.

    Article  CAS  Google Scholar 

  29. Motzkus D, Schulz-Maronde S, Heitland A, Schulz A, Forssmann WG, Jubner M et al. The novel β-defensin DEFB123 prevents lipopolysaccharide-mediated effects in vitro and in vivo. FASEB J 2006; 20: E997–E1004.

    Article  Google Scholar 

  30. Sun CQ, Arnold R, Fernandez-Golarz C, Parrish AB, Almekinder T, He J et al. Human β-defensin-1, a potential chromosome 8p tumor suppressor: control of transcription and induction of apoptosis in renal cell carcinoma. Cancer Res 2006; 66: 8542–8549.

    Article  CAS  Google Scholar 

  31. Shu Q, Shi Z, Zhao ZY, Chen Z, Yao HP, Chen QX et al. Protection against pseudomonas aeruginosa pneumonia and sepsis-induced lung injury by overexpression of β-defensin 2 in rats. Shock 2006; 26: 365–371.

    Article  CAS  Google Scholar 

  32. Fellermann K, Stange DE, Schaeffeler E, Schmalzl H, Wehkamp J, Bevins CL et al. A chromosome 8 gene-cluster polymorphism with low human beta-defensin 2 gene copy number predisposes to Crohn disease of the colon. Am J Hum Genet 2006; 79: 439–448.

    Article  CAS  Google Scholar 

  33. Levy MM, Fink MP, Marshall JC, Abraham E, Angus D, Cook D et al. 2001SCCM/ESICM/ACCP/ATS/SIS International sepsis definitions conference. Crit Care Med 2003; 31: 1250–1256.

    Article  Google Scholar 

Download references

Acknowledgements

This work was financially supported by National Natural Science Foundation of China (No. 30471662).

The authors disclose no financial interests that are relevant to the research or constitute a conflict of interest.

Author information

Authors and Affiliations

  1. Department of Anesthesiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, China

    Q-X Chen, C Lv, L-X Huang, B-L Cheng, G-H Xie, S-J Wu & X-M Fang

Authors
  1. Q-X Chen
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C Lv
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. L-X Huang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. B-L Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G-H Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S-J Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. X-M Fang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to X-M Fang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chen, QX., Lv, C., Huang, LX. et al. Genomic variations within DEFB1 are associated with the susceptibility to and the fatal outcome of severe sepsis in Chinese Han population. Genes Immun 8, 439–443 (2007). https://doi.org/10.1038/sj.gene.6364401

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gene.6364401

Keywords

This article is cited by

Search

Advanced search

Quick links