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  • Original Article
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Genetic, epidemiological and biological analysis of interleukin-10 promoter single-nucleotide polymorphisms suggests a definitive role for −819C/T in leprosy susceptibility

Genes & Immunity volume 10, pages 174–180 (2009)Cite this article

Abstract

Leprosy is a complex infectious disease influenced by genetic and environmental factors. The genetic contributing factors are considered heterogeneous and several genes have been consistently associated with susceptibility like PARK2, tumor necrosis factor (TNF), lymphotoxin-α (LTA) and vitamin-D receptor (VDR). Here, we combined a case–control study (374 patients and 380 controls), with meta-analysis (5 studies; 2702 individuals) and biological study to test the epidemiological and physiological relevance of the interleukin-10 (IL-10) genetic markers in leprosy. We observed that the −819T allele is associated with leprosy susceptibility either in the case–control or in the meta-analysis studies. Haplotypes combining promoter single-nucleotide polymorphisms also implicated a haplotype carrying the −819T allele in leprosy susceptibility (odds ratio (OR)=1.40; P=0.01). Finally, we tested IL-10 production in peripheral blood mononuclear cells stimulated with Mycobacterium leprae antigens and found that −819T carriers produced lower levels of IL-10 when compared with non-carriers. Taken together, these data suggest that low levels of IL-10 during the disease outcome can drive patients to a chronic and unprotective response that culminates with leprosy.

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Author notes

  1. A C Pereira and V N Brito-de-Souza: These authors contributed equally to this work.

Authors and Affiliations

  1. Instituto Lauro de Souza Lima, Bauru, São Paulo, Brazil

    A C Pereira, V N Brito-de-Souza, I M F Dias-Baptista, F P C Parelli, J Venturini & F R Villani-Moreno

  2. Departamento de Micobacterioses, Laboratório de Hanseníase, Instituto Oswaldo Cruz, Rio de Janeiro, Brazil

    C C Cardoso & M O Moraes

  3. Tropical Diseases Area, Botucatu Medical School, Sao Paulo State University, UNESP, Botucatu, São Paulo, Brazil

    F P C Parelli & J Venturini

  4. Departamento de Epidemiologia e Métodos Quantitativos em Saúde (DEMQS), Escola Nacional de Saúde Pública (ENSP)/PROCC, FIOCRUZ, Rio de Janeiro, Brazil

    A G Pacheco

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  1. A C Pereira
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Correspondence to M O Moraes.

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Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

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Pereira, A., Brito-de-Souza, V., Cardoso, C. et al. Genetic, epidemiological and biological analysis of interleukin-10 promoter single-nucleotide polymorphisms suggests a definitive role for −819C/T in leprosy susceptibility. Genes Immun 10, 174–180 (2009). https://doi.org/10.1038/gene.2008.97

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