title: NOD2 gene mutations associate weakly with ulcerative colitis but not with Crohn's disease in Indian patients with inflammatory bowel disease.
abstract: BACKGROUND
  Three mutations (two missense and one frameshift) in the NOD2 gene are associated with Crohn's disease (CD) in a proportion of patients with Crohn's disease in North America, Europe and Australia. These three mutations are not found in Indian patients with CD. We undertook new studies to identify polymorphisms in the NOD2 gene in the Indian population and to detect whether any of these were associated with inflammatory bowel disease (IBD) in this population.
  
  
  METHODS
  Individual exons of the NOD2 gene were amplified by PCR and subjected to denaturing high performance liquid chromatography (DHPLC) to detect heteroduplex formation. All 12 exons of the NOD2 gene were amplified and Sanger-sequenced to detect polymorphisms in the NOD2 gene. 310 patients with CD, 318 patients with ulcerative colitis (UC) and 442 healthy controls (HC) were recruited for association studies. DNA from these participants was evaluated for the identified eight polymorphisms by Sequenom analysis.
  
  
  RESULTS
  Heteroduplex formation was noted by DHPLC in exons 2 and 4 of the NOD2 gene. Sequencing of the entire NOD2 gene data revealed eight polymorphisms - rs2067085, rs2066842, rs2066843, rs1861759, rs2111235, rs5743266, rs2076753, and rs5743291 - of which the latter four were described for the first time in Indians. None of these polymorphisms was associated with CD. The SNPs rs2066842 and rs2066843 were in significant linkage disequilibrium. Both SNPs showed a significant association with UC (P=0.03 and 0.04 respectively; odds ratio 1.44 and 1.41 respectively).
  
  
  CONCLUSIONS
  Four NOD2 polymorphisms were identified for the first time in the Indian population. Of 8 NOD2 polymorphisms, none were associated with CD but two were weakly associated with UC. NOD2 polymorphisms do not play a major role in CD genesis in India.
authors.affiliation: Wellcome Trust Research Laboratory, Christian Medical College, Vellore 632004, India. pugazh@cmcvellore.ac.in
authors.forename: Srinivasan
authors.initials: S
authors.lastname: Pugazhendhi
authors.forename: Srikanth
authors.initials: S
authors.lastname: Santhanam
authors.forename: Jayanthi
authors.initials: J
authors.lastname: Venkataraman
authors.forename: Isabelle
authors.initials: I
authors.lastname: Creveaux
authors.forename: Balakrishnan S
authors.initials: BS
authors.lastname: Ramakrishna
mesh_terms: D000328:Adult; D003093:Colitis, Ulcerative / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D003424:Crohn Disease / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D006801:Humans; D007194:India / Q000453:epidemiology; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009154:Mutation; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein