Su1766 Phenotype of Peripheral T Lymphocyte Did Not Correlate With Genotype At rs7746082, a Confirmed Focal SNP on 6q21 for Crohn's Disease Susceptibility

Background: Pathogenesis of Crohn's disease (CD) is supposed to result from interactions between genetic predisposition, environmental triggers and mucosal immunity. The previous studies have highlighted the role of genetic predispositions, and several genes had been identified as important causing gene, such as NOD2/CARD15, IL23R, ATG16L1 and PTPN2. However, most of them might be rare and not be associated with susceptibility to CD in Chinese patients, suggesting possible genetic heterogeneity of CD in different populations. So far, no reports have determined the specific susceptibility genes in Chinese patients. Methods: In order to identify novel genetic variants associated to CD in Chinese patients, we performed exome sequencing in four Chinese individuals with CD, and further verified the variants using sanger sequencing. Then we validated the implicated variants in expanded additional cases including patients with CD, UC and healthy controls. Results: We uncovered 294 shared complete identical variants in four Chinese CD patients, of which 26 were validated with Sanger sequencing. Further analyzed the differences of genotype frequency between cases and controls, we detected 3 variants (IFNA10 c.60 T.A, IFNA4 c.60 T.A, PMS2P3 c.67 C.T) are associated with susceptibility to CD. The variants of IFNA10 and IFNA4 were significantly associated with resistance of steroids treatment in CD patients. Conclusion: We performed the exome-wide screening for the causative germline variants in Chinese Crohn's disease patients, identified three of new candidate gene variants of CD. These candidate genes may provide a clue to understand the genetic heterogeneity of CD and lead to better screening and improvement of treatment.