title: Variants of CARD15, TNFA and PTPN22 and susceptibility to Crohn's disease in the Czech population: high frequency of the CARD15 1007fs.
abstract: Crohn's disease (CD) has been shown to be associated with the variants in the CARD15 gene as well as in other genes involved in the immune response. The frequencies of the variants profoundly differ among populations and so does the associated risk. We examined the associations of variants in the CARD15, TNFA and PTPN22 genes with pediatric-onset and adult-onset CD in the Czech population. Genotype, phenotype and allelic frequencies were compared between 345 patients with CD (136 pediatric-onset and 209 adult-onset patients) and 501 unrelated healthy controls. At least one minor allele of the CARD15 gene was carried by 46% patients and only 21% control subjects (OR = 3.2, 95% CI 2.4-4.4). In a multiple logistic regression model, the strongest association with CD was found for the 1007fs variant (OR = 4.6, 95% CI 3.0-7.0), followed by p.G908R (OR = 2.9, 95% CI 1.5-5.7) and p.R702W (OR = 1.7, 95% CI 1.0-2.9), while no independent association was found for the remaining variants in the CARD15 gene (p.268S, p.955I and p.289S), for the p.R620W variant in the PTPN22 gene or for the g.-308G>A variant in the TNFA gene. The age at CD onset was strongly modified by positivity for the 1007fs allele: it was present in 42% pediatric-onset and only 25% adult-onset patients. In conclusion, we report a high frequency of the minor allele of the CARD15 1007fs polymorphism in the Czech population and a strong effect of this allele on the age at disease onset.
authors.affiliation: Department of Pediatrics, University Hospital Motol, Prague, Czech Republic.
authors.forename: O
authors.initials: O
authors.lastname: Hradsky
authors.forename: M
authors.initials: M
authors.lastname: Lenicek
authors.forename: P
authors.initials: P
authors.lastname: Dusatkova
authors.forename: J
authors.initials: J
authors.lastname: Bronsky
authors.forename: J
authors.initials: J
authors.lastname: Nevoral
authors.forename: V
authors.initials: V
authors.lastname: Valtrova
authors.forename: R
authors.initials: R
authors.lastname: Kotalova
authors.forename: P
authors.initials: P
authors.lastname: Szitanyi
authors.forename: R
authors.initials: R
authors.lastname: Petro
authors.forename: V
authors.initials: V
authors.lastname: Starzykova
authors.forename: M
authors.initials: M
authors.lastname: Bortlik
authors.forename: L
authors.initials: L
authors.lastname: Vitek
authors.forename: M
authors.initials: M
authors.lastname: Lukas
authors.forename: O
authors.initials: O
authors.lastname: Cinek
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D016022:Case-Control Studies; D002648:Child; D003424:Crohn Disease / Q000235:genetics* / Q000276:immunology; D018153:Czech Republic; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics* / Q000276:immunology; D010641:Phenotype; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22 / Q000235:genetics* / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000276:immunology
chemical_list: C429018:NOD2 protein, human; D053473:Nod2 Signaling Adaptor Protein; D014409:Tumor Necrosis Factor-alpha; C516765:PTPN22 protein, human; D054596:Protein Tyrosine Phosphatase, Non-Receptor Type 22