title: Common polymorphisms in the NOD2 gene region are associated with leprosy and its reactive states.
abstract: BACKGROUND
  Because of its wide spectrum of clinical manifestations and its well-defined immunological complications, leprosy is a useful disease for studying genetic regulation of the host response to infection. We hypothesized that polymorphisms in the nucleotide-binding oligomerization domain containing 2 (NOD2) gene, for a cytosolic receptor known to detect mycobacteria, are associated with susceptibility to leprosy and its clinical outcomes.
  
  
  METHODS
  We used a case-control study design with 933 patients in Nepal. Our study included 240 patients with type 1 (reversal) reactions and 124 patients with type 2 (erythema nodosum leprosum) reactions. We compared the frequencies of 32 common polymorphisms in the NOD2 gene region between patients with the different clinical types of leprosy as well as between the patients and 101 control participants without leprosy.
  
  
  RESULTS
  Four polymorphisms were associated with susceptibility to leprosy when comparing allele frequencies, and 8 were associated when comparing genotype frequencies with a dominant model. Five polymorphisms were associated with protection from reversal reaction in an allelic analysis, and 7 were associated with reversal reaction with a dominant model. Four polymorphisms were associated with increased susceptibility to erythema nodosum leprosum in an allelic analysis, whereas 7 of 32 polymorphisms were associated with a dominant model.
  
  
  CONCLUSIONS
  These data suggest that NOD2 genetic variants are associated with susceptibility to leprosy and the development of leprosy reactive states.
authors.affiliation: Dept of Medicine, University of Washington School of Medicine, 1959 NE Pacific St, Box 356523, Seattle, WA 98195, USA. berring@u.washington.edu
authors.forename: William Richard
authors.initials: WR
authors.lastname: Berrington
authors.forename: Murdo
authors.initials: M
authors.lastname: Macdonald
authors.forename: Saraswoti
authors.initials: S
authors.lastname: Khadge
authors.forename: Bishwa Raj
authors.initials: BR
authors.lastname: Sapkota
authors.forename: Marta
authors.initials: M
authors.lastname: Janer
authors.forename: Deanna Alisa
authors.initials: DA
authors.lastname: Hagge
authors.forename: Gilla
authors.initials: G
authors.lastname: Kaplan
authors.forename: Thomas Richard
authors.initials: TR
authors.lastname: Hawn
mesh_terms: D000328:Adult; D000483:Alleles; D016022:Case-Control Studies; D004893:Erythema Nodosum / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007918:Leprosy / Q000235:genetics*; D015440:Leprosy, Lepromatous / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009390:Nepal; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000502:physiology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein