BACKGROUND: Mycobacterium leprae is the etiologic pathogen that causes leprosy. The outcome of disease is dependent on the host genetic background. METHODS: We investigated the association of 51 single-nucelotide polymorphisms (SNPs) in anti-inflammatory cytokines (IL-10, TGFB1, IL-6, IL-4, and IL-13) and receptors (IL-10RA, IL-10RB, TGFBR1, TGFBR2, IL-6R, IL-4R, IL-5RA, IL-5RB, and IL-13RA1) with susceptibility to leprosy in a case-control study from New Delhi in northern India. This was followed by replication testing of associated SNPs in a geographically distinct and unrelated population from Orissa in eastern India. The functional potential of SNPs was established with in vitro reporter assays. RESULTS: Significant associations (P < .05) were observed for 8 polymorphisms (rs1800871, rs1800872, and rs1554286 of IL-10; rs3171425 and rs7281762 of IL-10RB; rs2228048 and rs744751 of TGFBR2; and rs1800797 of IL-6) with leprosy. This association was replicated for 4 SNPs (rs1554286 of IL-10, rs7281762 of IL-10RB, rs2228048 of TGFBR2, and rs1800797 of IL-6). The interaction study revealed a significantly greater association with leprosy risk than was obtained for any SNP individually. CONCLUSIONS: This study provides an interesting insight on the cumulative polygenic host component that regulates leprosy pathogenesis.
BACKGROUND:Mycobacterium leprae is the etiologic pathogen that causes leprosy. The outcome of disease is dependent on the host genetic background. METHODS: We investigated the association of 51 single-nucelotide polymorphisms (SNPs) in anti-inflammatory cytokines (IL-10, TGFB1, IL-6, IL-4, and IL-13) and receptors (IL-10RA, IL-10RB, TGFBR1, TGFBR2, IL-6R, IL-4R, IL-5RA, IL-5RB, and IL-13RA1) with susceptibility to leprosy in a case-control study from New Delhi in northern India. This was followed by replication testing of associated SNPs in a geographically distinct and unrelated population from Orissa in eastern India. The functional potential of SNPs was established with in vitro reporter assays. RESULTS: Significant associations (P < .05) were observed for 8 polymorphisms (rs1800871, rs1800872, and rs1554286 of IL-10; rs3171425 and rs7281762 of IL-10RB; rs2228048 and rs744751 of TGFBR2; and rs1800797 of IL-6) with leprosy. This association was replicated for 4 SNPs (rs1554286 of IL-10, rs7281762 of IL-10RB, rs2228048 of TGFBR2, and rs1800797 of IL-6). The interaction study revealed a significantly greater association with leprosy risk than was obtained for any SNP individually. CONCLUSIONS: This study provides an interesting insight on the cumulative polygenic host component that regulates leprosy pathogenesis.
Authors: M H T Stappers; Y Thys; M Oosting; T S Plantinga; M Ioana; P Reimnitz; J W Mouton; M G Netea; L A B Joosten; I C Gyssens Journal: Eur J Clin Microbiol Infect Dis Date: 2014-07-15 Impact factor: 3.267
Authors: Lucia Elena Alvarado-Arnez; Evaldo P Amaral; Carolinne Sales-Marques; Sandra M B Durães; Cynthia C Cardoso; Euzenir Nunes Sarno; Antonio G Pacheco; Francisco C F Lana; Milton Ozório Moraes Journal: PLoS One Date: 2015-09-04 Impact factor: 3.240
Authors: Rupali Chopra; Ponnusamy Kalaiarasan; Shafat Ali; Amit K Srivastava; Shweta Aggarwal; Vijay K Garg; Sambit N Bhattacharya; Rameshwar N K Bamezai Journal: BMJ Open Date: 2014-02-27 Impact factor: 2.692
Authors: N Lucena-Silva; M A G Teixeira; A de L Ramos; R S de Albuquerque; G T N Diniz; C T Mendes-Junior; E C Castelli; E A Donadi Journal: Mol Genet Genomic Med Date: 2013-06-07 Impact factor: 2.183