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Interleukin-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy

Abstract

We have determined IL-10 promoter genotypes of five single-nucleotide polymorphisms (SNPs): T−3575A, A−2849G, C−2763A, -A−1082G and C−819T. The haplotype frequencies were defined in healthy subjects compared to leprosy patients, and analyzed for their occurrence in multi- (MB) vs paucibacillary (PB) as severe and mild forms of leprosy, respectively. Haplotypes defined by three SNP positions (−3575, −2849 and −2763) captured significant differences between controls and patients (P=0.04). The haplotype carrying −3575A, −2849G and −2763C was associated with resistance to leprosy and to the development of severe forms of the disease using either a binomial (controls vs cases, P=0.005, OR=0.35, CI=0.13–0.91) or ordinal (controls vs PB vs MB, P=0.006, OR=0.32, CI=0.12–0.83) model. By contrast, the IL-10 haplotype −3575T/−2849A/−2763C was found to be associated with susceptibility to leprosy per se (P=0.027, OR=2.37, CI=1.04–5.39), but not leprosy type. The data suggest that the IL-10 locus contributes to the outcome of leprosy.

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References

  1. Fine PE, Sterne JA, Ponnighaus JM et al. Household and dwelling contact as risk factors for leprosy in northern Malawi. Am J Epidemiol 1997; 146: 91–102.

    Article  CAS  Google Scholar 

  2. Feitosa M, Krieger H, Borecki I, Beiguelman B, Rao DC . Genetic epidemiology of the Mitsuda reaction in leprosy. Hum Hered 1996; 46: 32–35.

    Article  CAS  Google Scholar 

  3. Ottenhoff THM, Verreck FAW, Lichtenauer-Kaligis EGR, Hoeve MA, Sanal O, Van Dissel JT . Genetics, cytokines and human infectious disease: lessons from weakly pathogenic mycobacteria and salmonellae. Nat Genet 2002; 32: 97–105.

    Article  CAS  Google Scholar 

  4. Fitness J, Tosh K, Hill AV . Genetics of susceptibility to leprosy. Genes Immun 2002; 3: 441–453.

    Article  CAS  Google Scholar 

  5. Mira MT, Alcais A, Van Thuc N et al. Chromosome 6q25 is linked to susceptibility to leprosy in a Vietnamese population. Nat Genet 2003; 33: 412–415.

    Article  CAS  Google Scholar 

  6. Mira MT, Alcaïs A, Thuc NV et al. A 5-prime regulatory region shared by the PARK2 and PACRG genes controls susceptibility to leprosy. Nature 2004; 427: 636–640.

    Article  CAS  Google Scholar 

  7. Jamieson SE, Miller EN, Black GF et al. Evidence for a cluster of genes on chromosome 17q11–q21 controlling susceptibility to tuberculosis and leprosy in Brazilians. Genes Immun 2004; 5: 46–57.

    Article  CAS  Google Scholar 

  8. Ottenhoff TH, Spierings E, Nibbering PH, de Jong R . Modulation of protective and pathological immunity in mycobacterial infections. Int Arch Allergy Immunol 1997; 113: 400–408.

    Article  CAS  Google Scholar 

  9. Lima MC, Pereira GM, Rumjanek FD et al. Immunological cytokine correlates of protective immunity and pathogenesis in leprosy. Scand J Immunol 2000; 51: 419–428.

    Article  CAS  Google Scholar 

  10. Misra N, Murtaza A, Walker B et al. Cytokine profile of circulating T cells of leprosy patients reflects both indiscriminate and polarized T-helper subsets: T-helper phenotype is stable and uninfluenced by related antigens of Mycobacterium leprae. Immunology 1995; 86: 97–103.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Eskdale J, Keijsers V, Huizinga T, Gallagher G . Microsatellite alleles and single nucleotide polymorphism (SNP) combine to form four major haplotype families at the human inteleukin-10 (IL-10) locus. Genes and Immun 1999; 1: 151–155.

    Article  CAS  Google Scholar 

  12. Gibson AW, Edberg JC, Wu J, Westerdorp RG, Huizinga TWJ, Kimberly RP . Novel single nucleotide polymorphisms in the distal IL-10 promoter affect IL-10 production and enhance the risk of systemic lupus erythematosus. J Immunol 2001; 166: 3915–3922.

    Article  CAS  Google Scholar 

  13. 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.

    Article  CAS  Google Scholar 

  14. Koss K, Satsangi J, Fanning GC, Welsh KI, Jewell DP . Cytokine (TNF alpha, LT alpha and IL-10) polymorphisms in inflammatory bowel diseases and normal controls: differential effects on production and allele frequencies. Genes Immun 2000; 1: 185–190.

    Article  CAS  Google Scholar 

  15. Ridley DS, Jopling WH . Classification of leprosy according to immunity—a five group system. Int J Lepr 1966; 34: 255–273.

    CAS  Google Scholar 

  16. Santos AR, Suffys PN, Vanderborght PR et al. Role of tumor necrosis factor-alpha and interleukin-10 promoter gene polymorphisms in leprosy. J Infect Dis 2002; 186: 1687–1691.

    Article  CAS  Google Scholar 

  17. Moraes MO, Santos AR, Schonkeren JJ et al. Interleukin-10 promoter haplotypes are differently distributed in the Brazilian versus the Dutch population. Immunogenetics 2003; 54: 896–899.

    CAS  Google Scholar 

  18. Schaid DJ, Rowland CM, Tines DE, Jacobson RM, Poland GA . Score tests for association between traits and haplotypes when linkage phase is ambiguous. Am J Hum Genet 2002; 70: 425–434.

    Article  Google Scholar 

  19. Terwilliger JD, Ott J (Eds) Linkage disequilibrium between alleles at marker loci. In: Handbook of Human Genetics Linkage. The John Hopkins University Press: Baltimore and London, 1994, pp 188–193.

    Google Scholar 

  20. Ihaka R, Gentleman R . A language for data analysis and graphics. J Comput Graph Stat 1996; 5: 299–314.

    Google Scholar 

  21. Miller EN, Jamieson SE, Joberty C et al. Genome-wide scans for leprosy and tuberculosis susceptibility genes in Brazilians. Genes Immun 2004; 5: 63–67.

    Article  CAS  Google Scholar 

  22. Editorial Freely associating. Nat Genet 1999; 22: 1–2.

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Acknowledgements

We are grateful to Valcemir F Silva-Filho for technical assistance and Denise Vieira for sample collection. These studies were supported in part by the World Health Organization/World Bank/TDR, the Netherlands Leprosy Foundation (NLR) and the Royal Netherlands Academy of Arts and Sciences (KNAW).

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Correspondence to MO Moraes.

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Moraes, M., Pacheco, A., Schonkeren, J. et al. Interleukin-10 promoter single-nucleotide polymorphisms as markers for disease susceptibility and disease severity in leprosy. Genes Immun 5, 592–595 (2004). https://doi.org/10.1038/sj.gene.6364122

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