Ilrb

Il23 Pathway

Cytoplasm Nucleus

Figure 9.26 Genetic associations with the IL23R pathway in Crohn's disease. Disease associations have been found for SNPs in genes encoding different proteins involved in this signalling pathway (indicated by asterixes) including the p40 subunit of IL23; the IL23R subunit of the IL23 receptor; Janus kinase 2 (JAK2), which is activated on receptor-ligand binding; and signal transducer and activator of transcription (STAT3), which is recruited, phosphorylated, homodimerized, and translocated into the nucleus to activate transcription. Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Immunology (Cho 2008), copyright 2008.

Cytoplasm Nucleus

Figure 9.26 Genetic associations with the IL23R pathway in Crohn's disease. Disease associations have been found for SNPs in genes encoding different proteins involved in this signalling pathway (indicated by asterixes) including the p40 subunit of IL23; the IL23R subunit of the IL23 receptor; Janus kinase 2 (JAK2), which is activated on receptor-ligand binding; and signal transducer and activator of transcription (STAT3), which is recruited, phosphorylated, homodimerized, and translocated into the nucleus to activate transcription. Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Immunology (Cho 2008), copyright 2008.

transcription 3), and JAK2 at chromosome 9p24 (encoding Janus kinase 2) were associated with Crohn's disease (Fig. 9.26) (Barrett et al. 2008). Strikingly, SNPs of IL12B and STAT3 were also associated with ulcerative colitis (Fisher et al. 2008; Franke et al. 2008). Potential common mechanisms underlying autoimmune disease are also underlined by the finding that SNPs in IL12B and IL23R are associated with psoriasis (Cargill et al. 2007) while an association study of 14 500 nonsynonymous

SNPs showed significant association between variation at IL23R and ankylosing spondylitis (Burton et al. 2007). This phenomenon is also observed for other Crohn's disease associated loci, for example PTPN2 was also associated with type 1 diabetes (WTCCC 2007) and 5q31 with psoriasis (Chang et al. 2008).

0 0

Post a comment