title: IL12B SNPs and copy number variation in IL23R gene associated with susceptibility to leprosy.
abstract: BACKGROUND
  Genome-wide studies have identified both human leucocyte antigen (HLA) and non-HLA regions in association with leprosy. Involvement of novel functional loci within these regions has been proposed by us earlier.
  
  
  METHODS
  We investigated the role of 23 single nucleotide polymorphisms (SNPs) in IL12B and IL12RB2 in a total of 2345 individuals from India, using MassArray platform, along with the copy number variations in IL23R, IL12RB2 and IL10 genes in a representative set of 257 individuals, using real-time PCR.
  
  
  RESULTS
  SNP rs2853694 in IL12B gene (AA vs AC+CC, p=2.6E-04, OR=1.42 (1.17-1.70)) showed an association with leprosy. Pairwise interaction analysis followed by combined analysis of multiple SNPs identified that IL12B, TNF and BTNL2-DRA inter-genic SNPs provided a major risk towards leprosy (p=2.6E-08, OR=3.94 (2.43-6.38)), showing a further increase (p=3.6E-14) for combined risk genotype interactions. On the other hand, IL12B, BAT1, NFKBIL1 and LTA SNPs together showed a disposition towards protection (p=0.000011, OR=0.32 (0.19-0.53)) with a further increase (p=6.38E-10) for combined protective genotype-interactions. Copy number variation analysis showed an increased copy number of the IL23R gene (PB=36.4%, controls=20.2%; p=0.026) associated with the pauci-bacillary form of leprosy, which correlated with a trend towards enhanced expression in memory T cells in a preliminary observation.
  
  
  CONCLUSIONS
  The observations made here highlight the importance of interaction between specific genetic backgrounds of immune response related genes in the outcome of Mycobacterium leprae infection.
authors.affiliation: National Centre of Applied Human Genetics, School of life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
authors.forename: Shafat
authors.initials: S
authors.lastname: Ali
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Srivastava
authors.forename: Rupali
authors.initials: R
authors.lastname: Chopra
authors.forename: Shweta
authors.initials: S
authors.lastname: Aggarwal
authors.forename: Vijay Kumar
authors.initials: VK
authors.lastname: Garg
authors.forename: Sambit Nath
authors.initials: SN
authors.lastname: Bhattacharya
authors.forename: Rameshwar Nath Koul
authors.initials: RN
authors.lastname: Bamezai
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D056915:DNA Copy Number Variations; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D007918:Leprosy / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D055815:Young Adult
chemical_list: C515500:IL23R protein, human; D053762:Interleukin-12 Subunit p40; D018123:Receptors, Interleukin