Association Analysis Of OCTN And DLG5 Genes Polymorphisms In Chinese Han Populations With Crhon's Disease

Background: Crohn's disease (CD) is an inflammatory bowel disease (IBD) characterized by chronic transmural, segmental and typically granulomatous inflammation of the gut. The pathogenesis of CD still remains unknown. It is accepted that CD is likely to be caused by combination of environmental, genetic, and immune factors in a genetically susceptible host. Recently some studies indicated that some genes may play an important role in determining the clinical phenotype of disease in addition to susceptibility. So defining candidate gene can we determine clinical phenotype according to the genotype.Peltekova and Stoll reported that two novel candidate genes loci associated with CD, SLC22A4 and SLC22A5 on chromosome 5 known as IBD5 and DLG5 on chromosome 10, were identified through association analysis of Caucasian CD patients. However , in Asia Yamazaki found that these candidate genes in Japanese patients with CD and found a weak but possible association with both SLC22A4 (P=0.028) and DLG5 (P=0.023).It is interesting to find out association of these gene polymorphisms in Chinese Han patients with Crhon's disease.Objective: To study the relationship of these genes and CD patients in Chinese Han population; to find OCTN gene SNPs associated with CD patients in Chinese Han population; to identify CD mechanism and analysis the relationship between genotypeand phenotype, individual treatment.Methods: Blood samples were obtained from 80 paients with CD, and 80 healthy controls in Shanghai location. To find out association of these gene polymorphisms in Chinese Han patients with Crhon's disease through PCR-RFLP. The characteristic of OCTN gene polymorphisms in Chinese patients with CD were found through DNA sequencing after purification.Results: 1) The report genetic variants that were indicated to be causative in the Caucasian population were completely absent in or were not associated with Chinese Han CD patients; 2) 30 patients with CD had OCTN1 (rs45488795) SNP and 41 patients with CD had OCTN2 (rs274558) SNP, which frequency was not significantly different with that of healthy controls. 3) Genotypes of OCTN1 (rs45488795) and OCTN2(rs274558) are associated with CD phenotype, 14 CD patients with OCTN1( rs45488795)(C/C) had their lesions in the terminal ileum (χ2=18.36,P=0.001), 18 CD patients with OCTN2(rs274558) (A/A) had their lesion in terminal ileum(χ2=14.70,,P=0.002),too, 39 CD patients with OCTN2(rs274558) (G/G) had their lesion in terminal ileum and colon(χ2=10.85,,P=0.013).Conclusion : 1) The reported genetic variants causative in the Caucasian population were completely absent in or were not associated with Chinese Han CD patients, 2) we do not found characteristic OCTN gene polymorphisms in Chinese Han patients with CD in Shanghai; OCTN1( rs45488795) and OCTN2(rs274558) SNPs were not associated with Chinese Han CD patients; 3) Genotypes of OCTN1( rs45488795) and OCTN2(rs274558) are associated with CD phenotype.