P131 NOD 2/CARD 15 GENE POLYMORPHISMS IN SERBIAN PATIENTS WITH CROHN'S DISEASE: GENOTYPE-PHENOTYPE ANALYSIS

Abstract

Background and aims: Pro-inflammatory cytokines may play a role in the pathogenesis of CD. The differential production of cytokines has been related to genetic polymorphisms in gene promoter regions. The aim of this case-control study was to assess the relationship between polymorphisms in cytokines genes and CD susceptibility as well as disease phenotype. Methods: 78 patients with CD and 102 controls were included in the study. 49 CD patients had inactive disease according to the Harvey-Bradshaw index (HBI) whereas the remaining 29 had an index 4-7.Cytokine genotyping was performed using PCR and PCR/RFLP. Gene polymorphisms that were probed for included IL-1beta-511C/T, IL-1beta+3953C/T, IL-1RaVNTR, TNFal-pha857C/T, TNFalpha308G/A, LTalpha+252A/G and IL-6-174G/C. Results: A significant association was observed between higher HBI and perforating disease (p=0.01) as well as disease onset >40 years (p=0.004). As compared to controls, we observed that carriers of the homozygous variant for TNFalpha857TT and for IL-6-174 CC had an increased risk for CD: OR 4.14 (95% IC 0.81-21.24) and OR 10.39 (95% IC 2.22-48.77), respectively. In respect to phenotype, significant associations were observed between TNFalpha857 polymorphism and the existence of perianal disease (p=0.002), recto-vaginal fistula (0.04), the presence of metabolic bone disease (p=0.05), as well as with age of disease onset (p=0.07). The latter was significantly associated to LTalpha +252 A/G and IL-6-174 G/C polymorphisms as well (p=0.05 and 0.04, respectively). Gender distribution in CD patients was associated to TNFal-pha308 polymorphism (p=0.004) whereas disease activity was significantly related to polymorphism in the sole anti-inflammatory cytokine analysed -IL-1RaVNTR (p=0.02).