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.

  • Original Article
  • Published:

Association of rs7719175, located in the IL13 gene promoter, with Schistosoma haematobium infection levels and identification of a susceptibility haplotype

Genes & Immunity volume 12, pages 31–39 (2011)Cite this article

Subjects

Abstract

Urinary schistosomiasis is a parasitic disease caused by Schistosoma haematobium helminths. S. haematobium eggs may remain trapped within the bladder or the ureter walls, causing major pathological disorders in the urogenital system. The polymorphism rs1800925(C/T) of the IL13 gene promoter, which is functional, has previously been associated with susceptibility to S. haematobium infection. The aim of this study was to further our understanding and to determine whether, in the 5q31-q33 region, rs1800925 affects infection levels alone or in synergy with other polymorphisms. After sequencing the IL13 promoter and increasing the single-nucleotide polymorphism density, we performed a linkage disequilibrium analysis between rs1800925 and the other markers in a Malian population. Multivariate linear regression analysis and electrophoretic mobility shift assay (EMSA) were performed to characterized markers in linkage disequilibrium with rs1800925. An additional polymorphism, rs7719175, in the IL13 promoter was associated with controlling infection levels in multivariate analysis. The haplotype rs7719175T-rs1800925C was associated with high infection levels. EMSA indicated that rs7719175 affects the binding of transcriptional factors to the promoter region. Polymorphisms rs7719175 and rs1800925 have a synergistic role in the control of infection levels caused by S. haematobium and using them as a haplotype allows a better discrimination between infected subjects.

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

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. van der Werf MJ, de Vlas SJ, Brooker S, Looman CW, Nagelkerke NJ, Habbema JD et al. Quantification of clinical morbidity associated with schistosome infection in sub-Saharan Africa. Acta Trop 2003; 86: 125–139.

    Article  Google Scholar 

  2. Abel L, Demenais F, Prata A, Souza AE, Dessein A . Evidence for the segregation of a major gene in human susceptibility/resistance to infection by Schistosoma mansoni. Am J Hum Genet 1991; 48: 959–970.

    CAS  PubMed  PubMed Central  Google Scholar 

  3. Marquet S, Abel L, Hillaire D, Dessein H, Kalil J, Feingold J et al. Genetic localization of a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31-q33. Nat Genet 1996; 14: 181–184.

    Article  CAS  Google Scholar 

  4. Marquet S, Abel L, Hillaire D, Dessein A . Full results of the genome-wide scan which localises a locus controlling the intensity of infection by Schistosoma mansoni on chromosome 5q31-q33. Eur J Hum Genet 1999; 7: 88–97.

    Article  CAS  Google Scholar 

  5. Muller-Myhsok B, Stelma FF, Guisse-Sow F, Muntau B, Thye T, Burchard GD et al. Further evidence suggesting the presence of a locus, on human chromosome 5q31-q33, influencing the intensity of infection with Schistosoma mansoni. Am J Hum Genet 1997; 61: 452–454.

    Article  CAS  Google Scholar 

  6. Dessein AJ, Begley M, Demeure C, Caillol D, Fueri J, dos Reis MG et al. Human resistance to Schistosoma mansoni is associated with IgG reactivity to a 37-kDa larval surface antigen. J Immunol 1988; 140: 2727–2736.

    CAS  PubMed  Google Scholar 

  7. Rihet P, Demeure CE, Bourgois A, Prata A, Dessein AJ . Evidence for an association between human resistance to Schistosoma mansoni and high anti-larval IgE levels. Eur J Immunol 1991; 21: 2679–2686.

    Article  CAS  Google Scholar 

  8. Demeure CE, Rihet P, Abel L, Ouattara M, Bourgois A, Dessein AJ . Resistance to Schistosoma mansoni in humans: influence of the IgE/IgG4 balance and IgG2 in immunity to reinfection after chemotherapy. J Infect Dis 1993; 168: 1000–1008.

    Article  CAS  Google Scholar 

  9. Couissinier-Paris P, Dessein AJ . Schistosoma-specific helper T cell clones from subjects resistant to infection by Schistosoma mansoni are Th0/2. Eur J Immunol 1995; 25: 2295–2302.

    Article  CAS  Google Scholar 

  10. Rodrigues Jr V, Piper K, Couissinier-Paris P, Bacelar O, Dessein H, Dessein AJ . Genetic control of schistosome infections by the SM1 locus of the 5q31-q33 region is linked to differentiation of type 2 helper T lymphocytes. Infect Immun 1999; 67: 4689–4692.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Hagan P, Blumenthal UJ, Dunn D, Simpson AJ, Wilkins HA . Human IgE, IgG4 and resistance to reinfection with Schistosoma haematobium. Nature 1991; 349: 243–245.

    Article  CAS  Google Scholar 

  12. Kouriba B, Chevillard C, Bream JH, Argiro L, Dessein H, Arnaud V et al. Analysis of the 5q31-q33 locus shows an association between IL13-1055C/T IL-13-591A/G polymorphisms and Schistosoma haematobium infections. J Immunol 2005; 174: 6274–6281.

    Article  CAS  Google Scholar 

  13. Gatlin MR, Black CL, Mwinzi PN, Secor WE, Karanja DM, Colley DG . Association of the gene polymorphisms IFN-gamma +874, IL-13 -1055 and IL-4 -590 with Patterns of Reinfection with Schistosoma mansoni. PLoS Negl Trop Dis 2009; 3: e375.

    Article  Google Scholar 

  14. He H, Isnard A, Kouriba B, Cabantous S, Dessein A, Doumbo O et al. A STAT6 gene polymorphism is associated with high infection levels in urinary schistosomiasis. Genes Immun 2008; 9: 195–206.

    Article  CAS  Google Scholar 

  15. van der Pouw Kraan TC, van Veen A, Boeije LC, van Tuyl SA, de Groot ER, Stapel SO et al. An IL-13 promoter polymorphism associated with increased risk of allergic asthma. Genes Immun 1999; 1: 61–65.

    Article  CAS  Google Scholar 

  16. Cameron L, Webster RB, Strempel JM, Kiesler P, Kabesch M, Ramachandran H et al. Th2 cell-selective enhancement of human IL13 transcription by IL13-1112C>T, a polymorphism associated with allergic inflammation. J Immunol 2006; 177: 8633–8642.

    Article  CAS  Google Scholar 

  17. The International HapMap consortium. The International HapMap project. Nature 2003; 426: 789–796.

    Article  Google Scholar 

  18. Thorisson GA, Smith AV, Krishnan L, Stein LD . The International HapMap project web site. Genome Res 2005; 15: 1592–1593.

    Article  CAS  Google Scholar 

  19. Frazer KA, Ballinger DG, Cox DR, Hinds DA, Stuve LL, Gibbs RA et al. A second generation human haplotype map of over 3.1 million SNPs. Nature 2007; 449: 851–861.

    Article  CAS  Google Scholar 

  20. Kouriba B, Traore HA, Dabo A, Sangare L, Guindo H, Keita AS et al. Urinary disease in 2 Dogon populations with different exposure to Schistosoma haematobium infection: progression of bladder and kidney diseases in children and adults. J Infect Dis 2005; 192: 2152–2159.

    Article  Google Scholar 

  21. Peisong G, Yamasaki A, Mao XQ, Enomoto T, Feng Z, Gloria-Bottini F et al. An asthma-associated genetic variant of STAT6 predicts low burden of ascaris worm infestation. Genes Immun 2004; 5: 58–62.

    Article  CAS  Google Scholar 

  22. Weidinger S, Gieger C, Rodriguez E, Baurecht H, Mempel M, Klopp N et al. Genome-wide scan on total serum IgE levels identifies FCER1A as novel susceptibility locus. PLoS Genet 2008; 4: e1000166.

    Article  Google Scholar 

  23. Brinkmann UK, Powollik W, Werler C, Traore M . An evaluation of sampling methods within communities and the validity of parasitological examination techniques in the field. Trop Med Parasitol 1988; 39: 162–166.

    CAS  PubMed  Google Scholar 

  24. Sambrook JE, Fritsch EF, Maniatis T . Molecular Cloning: A Laboratory Manual. 2nd edn. Cold Spring Harbor Laboratory Press: New York, 1989, pp 1.3–1.105.

    Google Scholar 

  25. Barrett JC, Fry B, Maller J, Daly MJ . Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics 2005; 21: 263–265.

    Article  CAS  Google Scholar 

  26. Jung H, Park J, Park Y, Kim Y, Kim K, Koh I . HapAnalyzer: minimum Haplotype analysis system for association studies. Genomics Inform 2004; 2: 107–109.

    Google Scholar 

Download references

Acknowledgements

We thank subjects for their participation in this study. We thank A Dessein for comments on the paper. This work received financial assistance from the Institut National de la Santé et de la Recherche Médicale, the World Health Organization (ID096546), the European Economic Community (TS3 CT940296, IC18CT970212), the Scientific and Technical Cooperation with Developing Countries (IC18CT980373), the French Ministere de la Recherche et des Techniques (PRFMMIP), the Conseil Général Provence Alpes Côte d’Azur and the Conseil Régional Provence Alpes Côte d’Azur. AI received a PhD fellowship from the French Ministere de la Recherche et de la Santé. We also thank Roy Riblet for English correction of this paper.

Author information

Authors and Affiliations

  1. INSERM, U906, Marseille, France

    A Isnard & C Chevillard

  2. Laboratory of Parasitology Mycology, Faculty of Medicine la Timone, University of Aix-Marseille, Marseille, France

    A Isnard & C Chevillard

  3. Department of Epidemiology and Parasitic Diseases, Faculty of Medicine, Pharmacy and Odonto-Stomatology, Bamako, Mali

    B Kouriba & O Doumbo

Authors
  1. A Isnard
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B Kouriba
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O Doumbo
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Chevillard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to C Chevillard.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Isnard, A., Kouriba, B., Doumbo, O. et al. Association of rs7719175, located in the IL13 gene promoter, with Schistosoma haematobium infection levels and identification of a susceptibility haplotype. Genes Immun 12, 31–39 (2011). https://doi.org/10.1038/gene.2010.43

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gene.2010.43

Keywords

This article is cited by

Search

Advanced search

Quick links