title: Association of NOD2 with Crohn's disease in a homogenous Irish population.
abstract: Linkage of IBD to the pericentromeric region of chromosome 16 has been widely confirmed by analyses of multiple populations. The NOD2 gene is located in the peak region of linkage on chromosome 16 and thought to be involved in the activation of nuclear factor (NF) kappaB in response to bacterial components. Mutations in the NOD2 gene are found to be strongly associated with susceptibility to Crohn's disease (CD). A total of 65 Irish CD families were genotyped to determine if NOD2 mutations conferred susceptibility to CD and the prevalence of these mutations in sporadic and familial forms of the disease. The Irish population is relatively homogenous and thus may provide advantages in genetic studies of complex diseases. We confirmed the IBD1 locus as a susceptibility locus for IBD within the Irish population by linkage analysis followed by linkage disequilibrium studies. No significant evidence of linkage was observed to the previously identified regions on chromosomes 1, 12 and 14. In all, 131 CD affected families were then genotyped for seven of the previously published NOD2 single-nucleotide polymorphisms (SNPs). Allelic transmission distortion was investigated using the pedigree disequilibrium test (PDT). SNP13 (3020insC) was found to be associated with CD (P=0.0186). Patients who possessed a rare allele of SNP8, 12 or 13 presented earlier when compared to patients without rare variants (mean age, 20.1 vs 24 years, P=0.011) and the rare allele of SNP13 was observed to be predominantly linked to ileal disease (P=0.02). This report confirms the importance of NOD2 as a susceptibility gene for CD within the Irish population.
authors.affiliation: Department of Medicine, University College Cork, Ireland.
authors.forename: Emer
authors.initials: E
authors.lastname: Bairead
authors.forename: Dawn L
authors.initials: DL
authors.lastname: Harmon
authors.forename: Anne M
authors.initials: AM
authors.lastname: Curtis
authors.forename: Yvette
authors.initials: Y
authors.lastname: Kelly
authors.forename: Clare
authors.initials: C
authors.lastname: O'Leary
authors.forename: Michelle
authors.initials: M
authors.lastname: Gardner
authors.forename: Dermot T
authors.initials: DT
authors.lastname: Leahy
authors.forename: Pat
authors.initials: P
authors.lastname: Vaughan
authors.forename: Denise
authors.initials: D
authors.lastname: Keegan
authors.forename: Colm
authors.initials: C
authors.lastname: O'Morain
authors.forename: Diarmuid
authors.initials: D
authors.lastname: O'Donoghue
authors.forename: Fergus
authors.initials: F
authors.lastname: Shanahan
authors.forename: Nollaig A
authors.initials: NA
authors.lastname: Parfrey
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Quane
mesh_terms: D000328:Adult; D000483:Alleles; D002352:Carrier Proteins / Q000235:genetics*; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D003424:Crohn Disease / Q000235:genetics*; D004252:DNA Mutational Analysis; D017931:DNA Primers; D005820:Genetic Testing; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D007494:Ireland; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D009154:Mutation / Q000235:genetics*; D053473:Nod2 Signaling Adaptor Protein; D010375:Pedigree
chemical_list: D002352:Carrier Proteins; D017931:DNA Primers; D047908:Intracellular Signaling Peptides and Proteins; C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein