Dorofeyev AE, Rassokhina OA, Kishenya MS, Derkach IA, Kiriyan EA, Sabodash EE
Background: Genetic predisposition is the key factor for inflammatory bowel diseases (IBD). NOD2/CARD15 (nucleotide-binding oligomerization domain family, member 2) is one of the most known genes in IBD and comes for clinical practice, especially Crohn?s disease (CD). For IBD predisposition analysis this gene mutations is useful and predict more aggressive disease course. NOD2/CARD15 is responsible for recognizing of pathogen-associated molecular patterns. Activation of Janus kinase-2 (JAK2) transcription pathway leads to expression of pro-inflammatory cytokines and induce immune response. JAK2 may be considered as a potential gene-candidate to IBD susceptibility. Genetic predisposition with polymorphism of NOD2/CARD15, JAK2 can play important role in pathogenesis of inflammatory bowel diseases. Aim: to characterize genetic susceptibility to ulcerative colitis (UC), Crohn?s disease (CD) in Ukranian cohort. Materials and methods: 115 IBD patients (58.3% UC and 41.7% CD) and 22 healthy controls were recruited. Single-nucleotide polymorphism (SNP) of NOD2/CARD15 (3020insC, Gly908Arg), JAK2 (Val617Phe) were determined by polymerase chain reaction (PCR) with electrophoretic detection in 3% agarose gel. Results: 72 (62.6%) IBD patients had NOD2/CARD15 single-nucleotide polymorphism. An association with CD for 3020insC was detected more often: 58.3% cases (p=0.001; OR=10.0; 95% CI=2.33-42.78), than with UC (37.3%, p=0.09). JAK2 mutations were revealed only in 11 (9.6%) patents with IBD and didn?t show any positive interaction with IBD. The interaction with SNPs and severity of IBD was revealed for CARD15 3020 insC. Conclusions: Important role of genetic predisposition in pathogenesis of IBD was revealed. Polymorphism of NOD2/CARD15 correlated with IBD in Ukranian cohort. More significant association with CD comparing to UC was determined for CARD15 (Gly908Arg). Patients with IBD had combined mutations of NOD2/CARD15, JAK2. Significant positive interaction between risk genes and the severity of CD and UC was determined.
