Die Rolle des CXCL9 Gens bei Kindern und Jugendlichen mit chronisch entzündlicher Darmerkrankung (CED)

Abstract

Genetic and environmental factors contribute to the etiopathology of Crohn’s disease (CD) and ulcerative colitis (UC). To identify early-onset susceptibility genes for inflammatory bowel disease, we measured the expression level of 88 genes from different biological contexts in colonic biopsies of pediatric patients and controls using real-time RT-PCR. We found that CXCL9 was highly expressed in the colonic tissue of 3/5 CD and 3/3 UC patients, but none of the controls. A subsequent SNP genotyping study on 114 Caucasian pediatric IBD patients and 120 ethnically matched unaffected adults for the 77147452G→A polymorphism of the CXCL9 gene (rs2276886) revealed a minor allele A frequency of 20.3 % in CD patients compared to 31.3 % in controls (p = 0.016) and 26.3 % in CU (ns). The clinical phenotype assessed by the Montreal classification was not related to the CXCL9 genotype. Children with homozygosity for the wild-type allele had an earlier onset of CD than heterozygous individuals (11.1 yrs vs 13.8 yrs; p = 0.0028). This is the first report of inverse association of the 77147452G→A polymorphism in the CXCL9 gene with pediatric CD. Our data may contribute to a better understanding of the pathophysiology underlying CD.