Frequency of single nucleotide polymorphisms in NOD1gene of ulcerative colitis patients: a case-control study in the Indian populationReportar como inadecuado

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BMC Medical Genetics

, 10:82

First Online: 01 September 2009Received: 28 September 2008Accepted: 01 September 2009


BackgroundEpidemiological studies have provided enough evidence that genetic factors have an important role in determining susceptibility to IBD. The most significant finding in the IBD research has been identification of mutations in the gene that encodes Nod2 nucleotide-binding oligomerization domain 2 protein in a subgroup of patients with Crohn-s disease. However, a very similar gene encoding Nod1 protein still has not been well documented for its association with Ulcerative colitis patients. Detection of polymorphism in NOD1 gene using SNP analysis has been attempted in the present study. We evaluated frequency and significance of mutations present in the nucleotide-binding domain NBD of NOD1 gene in context to Indian population.

MethodsA total of 95 patients with ulcerative colitis and 102 controls enrolled in the Gastroenterology department of All India Institute of Medical Sciences, New Delhi were screened for SNPs by DHPLC and RFLP techniques. Exon 6 locus in the NBD domain of NOD1 gene was amplified and sequenced. Genotype and allele frequencies of the patients and controls were calculated by the Pearson-s χ test, Fisher-s exact test and ANOVA with Bonferroni-s correction using SPSS software version 12.

ResultsWe have demonstrated DHPLC screening technique to show the presence of SNPs in Exon 6 locus of NBD domain of NOD1 gene. The DHPLC analysis has proven suitable for rapid detection of base pair changes. The data was validated by sequencing of clones and subsequently by RFLP analysis. Analyses of SNP data revealed 3 significant mutations W219R, p = 0.002; L349P, p = 0.002 and L370R, p = 0.039 out of 5 in the Exon 6 locus of NBD domain of the gene that encompasses ATP and Mgbinding sites. No significant association was observed within different sub phenotypes.

ConclusionWe propose that the location of mutations in the Exon 6 spanning the ATP and Mg binding site of NBD in NOD1 gene may affect the process of oligomerization and subsequent function of the LRR domain. Further studies are been conducted at the protein level to prove this possibility.

AbbreviationsNOD1Nuceotide oligomerization domain

UCUlcerative Colitis

NBDNucleotide Binding domain

IBDInflammatory Bowel Disease

SNPSingle Nucleotide Polymorphism.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2350-10-82 contains supplementary material, which is available to authorized users.

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Autor: Ravi Verma - Vineet Ahuja - Jaishree Paul


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