Abstract
To examine the contribution of interleukin-10 (IL-10) gene polymorphisms to Crohnos disease (CD) phenotype, and the possible genetic epistasis between IL-10 gene polymorphisms and CARD15/NOD2 gene mutations. A cohort of 205 Spanish unrelated patients with Crohn's disease recruited from a single center was studied. All patients were rigorously phenotyped and followed-up for at least 3 years (mean time, 12.5 years). The clinical phenotype was established prior to genotyping. The correlation of genotype-Vienna classification groups showed that the ileocolonic location was significantly associated with the -1082G allele in the NOD2/CARD15 mutation-positive patients (RR=1.52, 95%CI, 1.21 to 1.91, P=0.008). The multivariate analysis demonstrated that the IL-10 G14 microsatellite allele in the NOD2/CARD15 mutation positive patients was associated with two risk factors, history of appendectomy (RR=2.15, 95%CI=1.1-4.30, P=0.001) and smoking habit at diagnosis (RR=1.29, 95%CI=1.04-4.3, P=0.04). In Spanish population from Madrid, in CD patients carrying at least one NOD2/CARD15 mutation, the -1082G allele is associated with ileocolonic disease and the IL-10G14 microsatellite allele is associated with previous history of appendectomy and smoking habit at diagnosis. These data provide further molecular evidence for a genetic basis of the clinical heterogeneity of CD.
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