title: Detection of single-nucleotide polymorphisms in the intron 9 region of the nucleotide oligomerization domain-1 gene in ulcerative colitis patients of North India.
abstract: OBJECTIVE
  The nucleotide-binding oligomerization domain-1 (NOD1) gene encodes a pattern recognition receptor that senses pathogens. NOD1/caspase recruitment domain (CARD4) signaling leads to the activation of nuclear factor-kB, and plays an important role in innate immunity. Certain polymorphisms and mutations in NOD1/CARD4 might result in a dysfunctional innate immune response during bacterial recognition, which might have direct implications in inflammatory bowel disease (IBD) pathogenesis.
  
  
  METHODS
  We carried out a systemic analysis for the presence of polymorphic variants in the intron 9 region of the leucine-rich repeat (LRR) domain encompassing the exon-intron boundaries of the NOD1 gene. To detect unknown single-nucleotide polymorphisms, we used the denaturing high-performance liquid chromatography (DHPLC) screening technique and validated our data by restriction fragment length polymorphism and direct sequencing.
  
  
  RESULTS
  Genotype and allele frequencies showed significant differences in their distribution. The mutations discriminating alleles in the intron 9 region of the LRR domain of the NOD1 gene were correctly predicted by DHPLC technique and statistically verified in IBD and non-IBD individuals. Of the seven mutations detected, only four showed a significant association with disease activity. Mutations detected earlier in the exon 6 region of NOD1 were also used for the haplotype analysis. The GTTG haplotype was found to be significantly overrepresented in ulcerative colitis (UC) patients, as compared to the controls (P = 3.3726E(-6) ).
  
  
  CONCLUSIONS
  Our study has revealed a polymorphism association in the LRR domain of the NOD1 gene with the severity of UC disease. This might be due to disruption of the LRR region critical for NOD1-mediated bacterial sensing. A gene-wide, haplotype-based approach shows that GTTG haplotype carriers are overrepresented in UC patients, and that could increase the risk of the disease.
authors: School of Life Sciences, Jawaharlal Nehru University, New Delhi, India.
authors: Ravi
authors: R
authors: Verma
authors: Vineet
authors: V
authors: Ahuja
authors: Jaishree
authors: J
authors: Paul
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001483:Base Sequence; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D002851:Chromatography, High Pressure Liquid; D003093:Colitis, Ulcerative / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India; D007438:Introns; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics*; D010641:Phenotype; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D012720:Severity of Illness Index; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C119067:NOD1 protein, human; D053474:Nod1 Signaling Adaptor Protein