Γενετική προδιάθεση σε παιδιά με ιδιοπαθή φλεγμονώδη νόσο του εντέρου

Abstract

The present work aims to study genetic polymorphisms in Ulcerative Colitis (UC) and Crohn‘s Disease (CD) pediatric patients of Greek origin. To our knowledge this is the first attempt to search for genetic markers possibly involved in inflammatory bowel disease (IBD) development in pediatric patients of Greek ethnicity. Subjects studied and methods used: 125 Greek children with IBD (15 with UC and 110 with CD) aged 2.4 to 16.3 years at diagnosis as well as 659 healthy individuals of Greek origin used as controls were included in the study . Diagnosis of IBD was based on clinical, radiological, endoscopic and histological examination. Cytokines and cytokine receptors polymorphisms at the level of SNPs (IL1α-889, IL1β-511, IL1β+3962, IL1β-R pst 1 1970, IL1RA mspa1 11100, IL4-+1902, IL12-1188, TGFβ codon10, TGFβ codon25, TNFα-308, TNFα-238, IL2-330, IL2+166, IL4-1098, IL4-590, IL4-33,IL6-174, IL6 nt565, IL 10-1082, IL10-819 & IL10-592) were genotyped by PCR-SSP molecular technique (University of Heidelberg kit). Genetic polymorphisms of NOD2/CARD15 (R702W, G908R and 3020insC), ATG 16L1 (rs2241880A/G) and IL23R (rs11209026 (R381Q)) were also determined but only in children (No 110) with CD. PCR or PCR-RFLP technique was used for NOD2/CARD15 gene polymorphism analysis. ATG16L1 and IL23R gene polymorphisms were genotyped by PCR and melting curve analysis, using a pair of fluorescence resonance energy transfer (FRET) probes. Results 1. Statistically significant increase of IL-10 promoter phenotype-1082AG was found in patients with IBD (p=0.05), whereas a positive statically significant association (p=0.02) of IL-10 promoter phenotype -592CC was observed only in patients with CD. Regarding the IL-10 promoter haplotypes (1082G>A, -819T>C, -592A>C) only -1082AG phenotypes where found to predominate in IBD patients, in particular in UC patients. 2. The polymorphism 3020insC in NOD2/CARD15 was significantly higher in children with CD than in controls (p<0.0001). Association with at least 1 NOD2/CARD15 variant was specific for ileal disease with or without colonic involvement. 3. Genotype GG of ATG16L1 rs2241880 polymorphism was significantly higher in children with CD than in controls (p=0.019). 4. Genotype RQ of IL23R rs11209026 polymorphism was under represented in pediatric CD patients (p=0.012). 5. The presence of the rs2241880 ATG16L1 and rs11209026 IL23R polymorphisms, according to our findings, did not influence CD phenotype. Conclusion: Our results indicate that genetic polymorphisms involved in inflammatory immune response (ILs, NOD2/CARD15 and autophagy), contribute to IBD pathogenesis and could be used as genetic markers of IBD susceptibility.