Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01889 (ankylosing spondylitis)
 5,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An insertion mutation at nucleotide 3020 (3020insC) and a missense mutation G2722C in the CARD15 gene on chromosome 16p have been reported to be associated with Crohn's disease (CD). The protein encoded by the CARD15 gene is expressed in peripheral monocytes and regulates apoptosis and NF-kappaB activation, factors which play an important role in inflammation. Since CD and ankylosing spondylitis (AS) are interrelated disorders, we have investigated whether these mutations in the CARD15 gene are also associated with AS. We studied 113 unrelated AS patients and 152 unrelated healthy controls. No significant differences were found between patients and controls in the prevalence of the insertion 3020insC mutation and the G2722C missense mutation, OR = 1.36, 95% CI: 0.27-6.84, P = 0.70 and OR = 0.58; 95% CI: 0.18-1.94; P = 0.38, respectively. We conclude that the insertion 3020insC mutation and the G2722C missense mutation in the CARD15 gene are not involved in the susceptibility to AS.
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PMID:CARD15 gene mutations are not associated with ankylosing spondylitis. 1259 6

Peripheral involvement of the joints, including pauciarticular, asymmetrical, transitory and migrating synovitis and enthesiopathy, is observed in 10-20% of affected inflammatory bowel disease patients. Recurrence is common and frequently coincides with a flare-up of intestinal disease. The true prevalence of axial involvement is less well established. Sacroiliitis is a hallmark of spondylitis, but is under-reported due to its insidious onset and sometimes asymptomatic nature. Radiographic evidence of sacroiliitis is present in about 20-25% of patients. Ankylosing spondylitis, as defined by the Rome criteria, is present in 3-10% of inflammatory bowel disease patients, and is thought to have a different genetic predisposition in these patients compared with 'classic' ankylosing spondylitis: whereas the human leucocyte antigen B27 phenotype is present in 90% of patients with 'classic' ankylosing spondylitis, the prevalence decreases to only 30% in patients with ankylosing spondylitis secondary to Crohn's disease. Polymorphisms involving CARD15 appear to be a possible genetic trigger: 78% of patients with Crohn's disease and symptomatic or asymptomatic sacroiliitis carry at least one mutation, compared with only 48% of control Crohn's disease patients. Moreover, in other forms of spondyloarthropathy, a similar association has been reported: 42% of patients with spondyloarthropathy and associated asymptomatic chronic gut inflammation, who are considered likely to develop Crohn's disease and ankylosing spondylitis, are carriers of at least one CARD15 mutation, compared with only 7% of patients with normal histology. In addition to genetic markers, clinical features support the relationship between gut and joint pathophysiology. In cases of spondyloarthropathy, a very rapid, substantial and sustained improvement in symptoms has been reported following treatment with infliximab, suggesting an essential role for tumour necrosis factor-alpha in spondyloarthropathy, similar to that observed in Crohn's disease.
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PMID:Review article: joint involvement in inflammatory bowel disease. 1535 92

The spondyloarthropathies constitute a group of inflammatory joint diseases linked by shared characteristics that include a strong common genetic background. Genetic factors include major histocompatibility complex (MHC) genes, among which HLA-B27 contributes 30% of the overall genetic susceptibility to spondyloarthropathies, and non-MHC genes, none of which have been identified to date. Genome screens have identified regions that may contain susceptibility genes for spondyloarthropathies. In particular, a locus on the long arm of chromosome 9 (9q31-34) was identified by two groups working independently from each other. Studies using the candidate gene approach ruled out a role for most of the tested genes, including CARD15/NOD2. However, several independent groups have reported significant associations between ankylosing spondylitis and the IL-1 gene cluster on the long arm of chromosome 2.
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PMID:The genetics of spondyloarthropathies. 1665 Jul 94

Between 5 and 10% of cases of ankylosing spondylitis (AS) are associated with inflammatory bowel disease (IBD), either Crohn's disease or ulcerative colitis. A much larger percentage of AS patients have subclinical gut inflammation manifested either by endoscopic findings or by histology. The association with HLA-B27 is less strong in IBD-associated AS than in idiopathic AS, and there is evidence for an association between gut inflammation in AS with the Crohn's-disease-related CARD15 mutations. Despite the different genetics, the immunopathology suggests common inflammatory pathways in gut and joint inflammation in AS, and in gut inflammation in AS and IBD. Although this observation is of interest to unravel the pathophysiology of the disease, systematic screening of AS patients by ileocolonoscopy is not indicated in the absence of gut symptomatology as only a small proportion of AS patients with subclinical gut inflammation will develop overt IBD over time. Treatment of AS associated with IBD with non-steroidal anti-inflammatory drugs (NSAIDs) is problematic because of concerns of potential re-activation of IBD by NSAIDs. Major advances have been made in recent years with the establishment of anti-tumour necrosis factor (TNF) therapy in AS, the other spondyloarthritides and IBD. Anti-TNF agents are of particular relevance to AS patients with concomitant IBD who are at risk of exacerbation of the underlying bowel disease when treated with NSAIDs. In IBD, infliximab, unlike etanercept, is effective in treating clinical symptoms, inducing and maintaining remission, and mucosal healing. Adalimumab appears to be effective in treating both AS and IBD; however, official approval is pending. Currently, infliximab is the drug of choice for the treatment of patients with active AS associated with IBD.
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PMID:Ankylosing spondylitis and bowel disease. 1677 76