| セッション情報 |
Host-microbial Interaction and Immunology in IBD b. Clinical Aspects
|
| タイトル |
IF3b-1 Genetic Aspects of Host Immunity and Microbiota in IBD
|
| 演者 |
Stephan Schreiber（Department of Internal Medicine IChristian-Albrechts-UniversityGermany） |
| 共同演者 |
|
| 抄録 |
Heritable components have been suggested by analysis of the epidemiology of IBD long before they wereconfirmed through molecular discoveries． IBD represents a “complex disease” involving large numbers ofinteracting disease genes．In 2001 three coding variations in the NOD2 gene were identified as first disease genes． All variants affectthe leucin rich repeat part （LRR） of the encoded proteinthat is involved in bacteria induced activation ofNFkB in macrophages and epithelial cells． A particular subphenotype with more frequent ileocecal local－ization is associated with NOD2 variants． Variants in the NOD2 LRR are associated with a different colo－nic microbial flora in both mice and mentooVariants in the NOD2 gene do not explain the genetic risk for Crohn disease． More than 100 disease geneshave been identifiedwhich still only explain 20i30％ of the heritable risk． ln addition to innate immunebarrier genescytokine response genes （e．g． IL－23RIL12BSTAT3） and autophagy related genes （e．g．ATG 16LlIRGM） have been found． More than 50 disease genes are known in ulcerative． Some overlapwith Crohn disease whereas others（e．g． variants in the 3’1レ10 region）are unique to ullcerative colitis．The exploration of monozygoticdiscordant twins allows the dissection between genetic and non－geneticrisk factors． We find that a strong relationship exists between microbiota and colonic transcriptome innormal controis and even more in healthy twins． Howeverthis relationsship is uncoupled in discordanttwins indicating a primary role of microbiota in the causation of disease． Twin cohorts can be used tostudy epigenetic risk factors tooWe could indentify differential methylated regions through a genomewide analysis that result in causative mechanisms in addition to disease genes． |
| 索引用語 |
|
