Identification Of Susceptibility Genes And Their Functions For UC In Chinese By An EQTL-based Method

Ulcerative colitis(UC)is an idiopathic,chronic inflammatory disorder of the colonic mucosa. The precise cause of UC is unknown; however, genetically susceptible individuals seem to have a dysregulated mucosal immune response to commensal gut flora, which results in bowel inflammation. Epidemiologic research has found that,in western countries,the accidence rate of UC is higher than that in Asian; Jews have a rate of ulcerative colitis that is two to four times higher than that of other ethnic groups. The risk is particularly high in first-degree relatives:5.7–15.5% of patients with ulcerative colitis have a first-degree relative with the same disease; And monozygotic twins have concordance rates for ulcerative colitis of 6–13%.This shows a strong hereditary susceptibility contribution to UC.Recently,genome-wide association analysis found that IBD susceptibility locus distributed on 13 chromosomes. Due to the genetic heterogeneity,there is a big difference between eastern and western populations. Been reported,CARD15(also called NOD2)、IL23R and ATG16L1 are associated with Crohn disease in Europe and North America,whereas there is no relationship in the Japanese population. A GWAS study identified a number of UC susceptibility loci in Japanese population and these sites have not been reported in Western populations. Therefore, find our UC population susceptibility locus as the current problems to be solved. Currently,there are 9 GWAS studies of UC, GWAS and a recent meta-analysis has identified 47 UC susceptibility locus, but these susceptibility locus whether located in intron,or located in intergenic regions or is synonymous variation, its functions are also speculated,and the pathogenesis of UC has not been determined.The genetic loci associated with the expression traits are termed eQTLs(expression quantitative trait loci).eQTL analysis treat the level of gene expression as a quantitative trait,and analyze the chromosomes which affect the gene expression to determine the level of gene expression.eQTL can determine the susceptibility genes.So we use this method to find susceptibility genes in our population.Objective 1.To establish differentially expressed genes of UC. 2.Through eQTL analysis to identify the feasibility of the follow experiment.Methods The Agilent Whole Human Genome Oligo Microarray were used for a differential expression profiles from 24 UC patients and 24 controls.And accord gene ontology enrichment analysis and pathway analysis to find susceptibility genes of UC.Accord to eQTL analysis provided by R,analyze Han SNP database and expression profile data to identify the feasibility of the follow experiment.Results 1.4132 genes were differentially expressed in gene profile of UC,2004 were up-regulated and 2128 down-regulated.2.Through the eQTL packet provided by R,combine the Han people SNP database and expression profiling data,to analyze the feasibility of the follow experiment.Conclusion Through the eQTL analysis to identify the susceptibility genes is feasible.It provides a new idea for our follow experiment.