title: Common variants in NOD2 and IL23R are not associated with inflammatory bowel disease in Indians.
abstract: OBJECTIVE
  Ulcerative colitis (UC) and Crohn's disease (CD) are two major phenotypes of inflammatory bowel disease (IBD) that present with inflammation of the colon or the entire gastrointestinal tract, respectively. Genome-wide association studies have confirmed the role of nucleotide-binding oligomerization domain protein-2 (NOD2) variants and identified several other genes associated with IBD. We investigated whether variants in NOD2 and interleukin-23 receptor (IL23R) are associated with IBD in a well-characterized case-control cohort from southern India.
  
  
  METHODS
  We recruited 652 patients (411 UC and 241 CD) using established diagnostic criteria and 442 age-, sex-, and ethnically-matched, normal individuals. By direct sequencing, we screened the complete NOD2 gene and genotyped the R381Q variant in IL23R, and performed an association analysis and genotype-phenotype correlation analysis.
  
  
  RESULTS
  The clinical presentation of UC and CD patients did not differ significantly from the Europeans. We observed a monomorphic status for three common disease-susceptible variants, R702W, G908R, and 1007fs in NOD2; three other single nucleotide polymorphisms, P268S, R459R, and R587R, had a comparable minor allele frequency in patients and controls. Compared to Europeans, we found a low frequency (∼1%) of the protective allele at R381Q in IL23R and no statistically-significant association with IBD (odds ratio = 0.87; 95% confidence interval = 0.26-2.86; P>0.05).
  
  
  CONCLUSIONS
  Our study suggests that variants in the NOD2 gene and the protective variant R381Q in IL23R are not associated with IBD in Indians. Additional variants in these or other candidate genes might play a major role in the pathophysiology of IBD in Indians.
authors.affiliation: Centre for Cellular and Molecular Biology, Hyderabad, India.
authors.forename: Swapna
authors.initials: S
authors.lastname: Mahurkar
authors.forename: Rupa
authors.initials: R
authors.lastname: Banerjee
authors.forename: Vasantha S
authors.initials: VS
authors.lastname: Rani
authors.forename: Nikita
authors.initials: N
authors.lastname: Thakur
authors.forename: Guduru Venkat
authors.initials: GV
authors.lastname: Rao
authors.forename: Duvvuru Nageshwar
authors.initials: DN
authors.lastname: Reddy
authors.forename: Giriraj R
authors.initials: GR
authors.lastname: Chandak
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003093:Colitis, Ulcerative / Q000208:ethnology / Q000235:genetics*; D003424:Crohn Disease / Q000208:ethnology / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007194:India / Q000453:epidemiology; D007223:Infant; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018123:Receptors, Interleukin / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D044465:White People / Q000235:genetics*; D055815:Young Adult
chemical_list: C515500:IL23R protein, human; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D018123:Receptors, Interleukin