title: Genetic variations and interactions in anti-inflammatory cytokine pathway genes in the outcome of leprosy: a study conducted on a MassARRAY platform.
abstract: 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.affiliation: National Centre of Applied Human Genetics, School of Life Sciences, Jawaharlal Nehru University, Delhi, India.
authors.forename: Shweta
authors.initials: S
authors.lastname: Aggarwal
authors.forename: Shafat
authors.initials: S
authors.lastname: Ali
authors.forename: Rupali
authors.initials: R
authors.lastname: Chopra
authors.forename: Amit
authors.initials: A
authors.lastname: Srivastava
authors.forename: Ponnusamy
authors.initials: P
authors.lastname: Kalaiarasan
authors.forename: Dheeraj
authors.initials: D
authors.lastname: Malhotra
authors.forename: Sailesh
authors.initials: S
authors.lastname: Gochhait
authors.forename: Vijay K
authors.initials: VK
authors.lastname: Garg
authors.forename: S N
authors.initials: SN
authors.lastname: Bhattacharya
authors.forename: Rameshwar N K
authors.initials: RN
authors.lastname: Bamezai
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D016207:Cytokines / Q000235:genetics* / Q000276:immunology*; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006239:Haplotypes; D054884:Host-Pathogen Interactions; D006801:Humans; D007194:India; D007918:Leprosy / Q000235:genetics* / Q000276:immunology*; D015810:Linkage Disequilibrium; D016015:Logistic Models; D009166:Mycobacterium leprae / Q000276:immunology*; D020641:Polymorphism, Single Nucleotide; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D016207:Cytokines