Genetics of Spondyloarthropathies and Inflammatory Bowel Disease: Searching for Common Susceptibility Factors

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http://www.ingentaconnect.com/content/ben/crr/2008/00000004/00000001/art00003;jsessionid=2a5uaypcpxu6y.henrietta

Genetics of Spondyloarthropathies and Inflammatory Bowel Disease: Searching for Common Susceptibility Factors

Authors: Laukens, Debby; Vos, e D.

Source: Current Rheumatology Reviews, Volume 4, Number 1, February 2008 , pp. 12-22(11)

Publisher: Bentham Science Publishers

Abstract:Ileocolonoscopic evidence for subclinical gut inflammation is found in a subpopulation of spondyloarthropathy (SpA) patients. The prevalence of microscopic intestinal lesions is even higher and can be classified as either an acute or a chronic type of inflammation. The latter condition is associated with an increased risk of developing overt inflammatory bowel disease (IBD), especially Crohn's disease (CD), over time. Evidence for genetic predisposition in both SpA and IBD is strong, and has resulted in the identification of several linked chromosomal loci and putative candidate genes. The regular co-existence of SpA and IBD within the same family suggests a common genetic component. Interestingly, comparison of genome-wide linkage and association data reveals thirteen disease-associated chromosomal regions that are shared between SpA and IBD. This should convince geneticists to examine genes within these regions as potential susceptibility genes for the development of both SpA and IBD. Significant association of such shared genetic determinants was established for NOD2 (16q), the major histocompatibility complex I allele HLA-B27 (6p) and recently also the interleukin 23 receptor (1p). Transgenic animals in which tumor necrosis factor alpha or HLA-B27 is overexpressed suffer both joint and gut abnormalities resembling human SpA/CD pathology, providing additional evidence for a common genetic predisposition for the onset of joint and gut inflammation. In view of a hypothetical pathway leading to intestinal and articular inflammation in SpA and IBD, we review and compare genome-wide linkage and genetic association data obtained for SpA and IBD.

Keywords: Spondyloarthropathy; Crohn's disease; genetic susceptibility; NOD2; HLA-B27; IL23R

Document Type: Research article