Abstract
Interleukin (IL)-10 is a regulatory cytokine of the helper T cell type 2 (TH2) pathway, which underlies both the host defense to helminthic infection and atopic diseases, including asthma. Although IL10 promoter polymorphisms are associated with increased atopy risk, IL10 variation has not been thoroughly explored in schistosomiasis-endemic populations. Three atopy-related IL10 promoter polymorphisms (rs1800896, rs1800871 and rs1800872), complemented by six tagging single-nucleotide polymorphisms (SNPs), were genotyped in 812 individuals in 318 nuclear families from a schistosomiasis-endemic area in Brazil. Associations between markers and total serum Immunoglobulin E (tIgE) levels, indicating non-specific activation of the TH2 pathway, and Schistosoma mansoni fecal egg counts, indicating burden of infection reflecting effectiveness of schistosomiasis host immunity, were performed using family-based transmission disequilibrium tests for quantitative traits (QTDTs). Alleles A, T and A at the three promoter SNPs rs1800896, rs1800871 and rs1800872 were associated with high tIgE levels in the same direction as in atopy populations (P=0.0008, 0.026 and 0.045), but not with egg counts. IL10 promoter polymorphisms appear to influence non-specific tIgE levels, but not schistosomiasis-specific immunity. The tagging SNP rs3024495 was associated with high S. mansoni egg counts (P=0.005), suggesting a novel locus in IL10 may influence clinically relevant burden of infection.
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References
King CH, Dickman K, Tisch DJ . Reassessment of the cost of chronic helmintic infection: a meta-analysis of disability-related outcomes in endemic schistosomiasis. Lancet 2005; 365: 1561–1569.
Quinnell RJ . Genetics of susceptibility to human helminth infection. Int J Parasitol 2003; 33: 1219–1231.
Caldas IR, Campi-Azevedo AC, Oliveira LF, Silveira AM, Oliveira RC, Gazzinelli G . Human schistosomiasis mansoni: immune responses during acute and chronic phases of the infection. Acta Trop 2008; 108: 109–117.
Pearce EJ, MacDonald AS . The immunobiology of schistosomiasis. Nat Rev Immunol 2002; 2: 499–511.
Belkaid Y, Blank RB, Suffia I . Natural regulatory T cells and parasites: a common quest for host homeostasis. Immunol Rev 2006; 212: 287–300.
Robinson DS, Larche M, Durham SR . Tregs and allergic disease. J Clin Invest 2004; 114: 1389–1397.
Alves Oliveira LF, Moreno EC, Gazzinelli G, Martins-Filho OA, Silveira AM, Gazzinelli A et al. Cytokine production associated with periportal fibrosis during chronic schistosomiasis mansoni in humans. Infect Immun 2006; 74: 1215–1221.
de Morais CN, Rodrigues de Souza J, Gomes de Melo W, Aroucha ML, Domingues AL, Wynn T et al. Studies on the production and regulation of interleukin, IL-13, IL-4 and interferon-gamma in human Schistosomiasis mansoni. Mem Inst Oswaldo Cruz 2002; 97 (Suppl 1): 113–114.
Silva-Teixeira DN, Contigli C, Lambertucci JR, Serufo JC, Rodrigues Jr V . Gender-related cytokine patterns in sera of schistosomiasis patients with Symmers’ fibrosis. Clin Diagn Lab Immunol 2004; 11: 627–630.
de Jesus AR, Magalhaes A, Miranda DG, Miranda RG, Araujo MI, de Jesus AA et al. Association of type 2 cytokines with hepatic fibrosis in human Schistosoma mansoni infection. Infect Immun 2004; 72: 3391–3397.
Capron A, Dombrowicz D, Capron M . Helminth infections and allergic diseases: from the th2 paradigm to regulatory networks. Clin Rev Allergy Immunol 2004; 26: 25–34.
van den Biggelaar AH, van Ree R, Rodrigues LC, Lell B, Deelder AM, Kremsner PG et al. Decreased atopy in children infected with Schistosoma haematobium: a role for parasite-induced interleukin-10. Lancet 2000; 356: 1723–1727.
Araujo MI, Hoppe B, Medeiros Jr M, Alcantara L, Almeida MC, Schriefer A et al. Impaired T helper 2 response to aeroallergen in helminth-infected patients with asthma. J Infect Dis 2004; 190: 1797–1803.
Lynch NR, Hagel I, Perez M, Di Prisco MC, Lopez R, Alvarez N . Effect of anthelmintic treatment on the allergic reactivity of children in a tropical slum. J Allergy Clin Immunol 1993; 92: 404–411.
Medeiros Jr M, Figueiredo JP, Almeida MC, Matos MA, Araujo MI, Cruz AA et al. Schistosoma mansoni infection is associated with a reduced course of asthma. J Allergy Clin Immunol 2003; 111: 947–951.
Ober C, Hoffjan S . Asthma genetics 2006: the long and winding road to gene discovery. Genes Immun 2006; 7: 95–100.
Bethony JM, Quinnell RJ . Genetic epidemiology of human schistosomiasis in Brazil. Acta Trop 2008; 108: 166–174.
Turner DM, Williams DM, Sankaran D, Lazarus M, Sinnott PJ, Hutchinson IV . An investigation of polymorphism in the interleukin-10 gene promoter. Eur J Immunogenet 1997; 24: 1–8.
Grant AV, Araujo MI, Ponte EV, Oliveira RR, Cruz AA, Barnes KC et al. High heritability but uncertain mode of inheritance for total serum IgE level and Schistosoma mansoni infection intensity in a schistosomiasis-endemic Brazilian population. J Infect Dis 2008; 198: 1227–1236.
Azevedo ES . Subgroup studies of black admixture within a mixed population of Bahia, Brazil. Ann Hum Genet 1980; 44 (Part 1): 55–60.
Katz N, Coelho PM, Pellegrino J . Evaluation of Kato's quantitative method through the recovery of Schistosoma mansoni eggs added to human feces. J Parasitol 1970; 56: 1032–1033.
Katz N, Zicker F, Rocha RS, Oiveira VB . Reinfection of patients in schistosomiasis mansoni endemic areas after specific treatment. Rev Inst Med Trop Sao Paulo 1978; 20: 273–278.
de Bakker PI, Yelensky R, Pe’er I, Gabriel SB, Daly MJ, Altshuler D . Efficiency and power in genetic association studies. Nat Genet 2005; 37: 1217–1223.
International HapMap Consortium. A haplotype map of the human genome. Nature 2005; 437: 1299–1320.
Gabriel SB, Schaffner SF, Nguyen H, Moore JM, Roy J, Blumenstiel B et al. The structure of haplotype blocks in the human genome. Science 2002; 296: 2225–2229.
Eichenbaum-Voline S, Baur MP, Knapp M . Genetic analysis of a complex disease in the presence of an environmental risk factor. Genet Epidemiol 1999; 17 (Suppl 1): S545–S550.
Howard TD, Whittaker PA, Zaiman AL, Koppelman GH, Xu J, Hanley MT et al. Identification and association of polymorphisms in the interleukin-13 gene with asthma and atopy in a Dutch population. Am J Respir Cell Mol Biol 2001; 25: 377–384.
Abecasis GR, Cardon LR, Cookson WO . A general test of association for quantitative traits in nuclear families. Am J Hum Genet 2000; 66: 279–292.
Hobbs K, Negri J, Klinnert M, Rosenwasser LJ, Borish L . Interleukin-10 and transforming growth factor-beta promoter polymorphisms in allergies and asthma. Am J Respir Crit Care Med 1998; 158: 1958–1962.
Acknowledgements
We thank the people of the endemic area in Conde from Buri, Camarao, Genipapo, Sempre Viva and Cobo for their participation in our study, the health liaisons, Adaliudes Conceição, Luciana Quintela, Ivanice Santos, the public health officers of the main Conde office, Analú Lima, Benivaldo Valber Oliveira Silva and Iraci Santos Araujo and students from the Federal University of Bahia who assisted in data collection, Rafael Santana, Roberta Barbosa, Ana Paula Santana, Charlton Barros, Marcele Bradão, Ludmila Almeida, Thiago Cardoso and Daniela Costa. We also thank Tracy Hand, Peisong Gao, Monica Campbell and Itael Evgey for conducting all of the genotyping experiments. Thanks to Dani Fallin and Alan Scott for helpful discussions, and to Priya Duggal and Sabine Plancoulaine for critical reading of the paper. This research was supported by Glaxo-Smith-Kline under the project WE445 entitled ‘Immunogenetics of Schistosomiasis and Asthma,’ and NIH grant # AI050024. KCB was supported in part by the Mary Beryl Patch Turnbull Scholar Program.
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Grant, A., Araujo, M., Ponte, E. et al. Polymorphisms in IL10 are associated with total Immunoglobulin E levels and Schistosoma mansoni infection intensity in a Brazilian population. Genes Immun 12, 46–50 (2011). https://doi.org/10.1038/gene.2010.50
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DOI: https://doi.org/10.1038/gene.2010.50
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