Genotypic interaction and gender specificity of common genetic variants in the p53/mdm2 network in Crohn's disease.
Digestion
; 81(4): 246-51, 2010.
Article
em En
| MEDLINE
| ID: mdl-20110711
ABSTRACT
BACKGROUND/AIMS:
Defective p53-mediated apoptosis and cell cycle control have been implicated in the immunopathogenesis of Crohn's disease (CD). Since common functional variants of p53 (SNP72 G/C) and its key negative regulator mdm2 (SNP309 T/G) have been reported to affect cellular apoptotic and cell cycle arrest capacities, we assessed the effects of these variants on CD susceptibility and their relationship to NOD2/CARD15 as a well-established genetic CD risk factor.METHODS:
The variants SNP72 G/C and SNP309 T/G were genotyped in 149 European CD patients and 478 healthy controls. Subgroup analysis was performed in relation to NOD2/CARD15 status and to demographic/clinical characteristics.RESULTS:
The p53 SNP72 CC genotype tended to be less frequent in CD. This reached statistical significance only in the male cohort (0 vs. 7.3%; p = 0.037). Genotype and allele frequencies of both single-nucleotide polymorphisms (SNPs) were otherwise not significantly different. In the combined genotypic analysis, the genotype p53 SNP72 CC was significantly underrepresented in mdm2 SNP309 TT homozygotes (0 vs. 9.7%; p = 0.034). No association was observed between NOD2/CARD15 and the respective SNPs.CONCLUSION:
We report on a gender-specific protective effect of the low-apoptotic SNP72 CC genotype, and a gender-unrestricted genotypic interaction between SNP309 TT and SNP72 CC, which, for the first time, links sequence variation of the p53/mdm2 network to CD, independent of NOD2/CARD15.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Doença de Crohn
/
Proteína Supressora de Tumor p53
/
Apoptose
/
Predisposição Genética para Doença
/
Proteínas Proto-Oncogênicas c-mdm2
Tipo de estudo:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Digestion
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Alemanha