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)

We have genotyped 14,436 nonsynonymous SNPs (nsSNPs) and 897 major histocompatibility complex (MHC) tag SNPs from 1,000 independent cases of ankylosing spondylitis (AS), autoimmune thyroid disease (AITD), multiple sclerosis (MS) and breast cancer (BC). Comparing these data against a common control dataset derived from 1,500 randomly selected healthy British individuals, we report initial association and independent replication in a North American sample of two new loci related to ankylosing spondylitis, ARTS1 and IL23R, and confirmation of the previously reported association of AITD with TSHR and FCRL3. These findings, enabled in part by increased statistical power resulting from the expansion of the control reference group to include individuals from the other disease groups, highlight notable new possibilities for autoimmune regulation and suggest that IL23R may be a common susceptibility factor for the major 'seronegative' diseases.
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PMID:Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. 1795 73

Spondylarthropathies revolve around the strongest known contributing factor, HLA-B27. However, the role of HLA-B27 remains unclear. Its subtypes are reported here in the particular context of developing countries. Non-MHC factors are also being described. The role of immunity is being elucidated. Cytokine expression has been proved to play a major role in ankylosing spondylitis (AS). Recently shown are IL23R, which encodes a critical cytokine receptor in the TH17 subset of T cells, and ARTS1, loss of function of which could have pro-inflammatory effects. This constitutes a major breakthrough in the understanding of AS which could potentially lead to a therapy. New imaging techniques and therapies have substantially improved the earlier diagnosis and management of the disease. However, criteria for an early diagnosis remain to be settled. Such criteria are particularly important for developing countries where they could help in decreasing the socioeconomic burden of the disease.
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PMID:Ankylosing spondylitis and reactive arthritis in the developing world. 1878 46

Major advances have been achieved over the last 10 years both in the clinical and scientific understanding of the spondyloarthritides (SpA), which can be separated in predominantly axial and predominantly peripheral SpA. The clinical progress includes the development of classification criteria, strategies for early diagnosis, definition of outcome criteria for clinical studies, and the conduction of a series of clinical studies with a focus on tumor necrosis factor (TNF) blockers. The proven high efficacy of TNF blocker treatment has meant a breakthrough for SpA patients, who until recently had only quite limited treatment options. More and more data have accumulated over recent years in regard to long-term efficacy and safety, prediction of response, and the relevance of extrarheumatic manifestations such as uveitis, psoriasis, and inflammatory bowel disease for treatment decisions with TNF blockers. A better understanding of the interaction of the immune system and inflammation with bone degradation/new bone formation is crucial for the development of optimal treatment strategies to prevent structural damage. Recent results from genetic studies could show that, besides HLA-B27, the interleukin-23 receptor and the ARTS1 enzyme are associated with ankylosing spondylitis. Only when the exact pathogenesis is clarified will a curative treatment be possible.
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PMID:Developments in the scientific and clinical understanding of the spondyloarthritides. 1923 62

It has long been known that the major histocompatibility complex (MHC) is essentially involved in genetic susceptibility to ankylosing spondylitis (AS). The HLA-B27 antigen has been accounted for 20 to 50% of the total genetic risk for this disease. However, susceptibility to AS cannot be fully explained by associations with the MHC. Recent studies including linkage analyses as well as candidate gene and, most recently, genome-wide association studies indicate significant associations of the interleukin-1 gene cluster, interleukin-23 receptor and ARTS1 genes as well as other possible loci with AS. In the murine model of proteoglycan-induced spondylitis, two susceptibility loci termed Pgis1 and Pgis2 were identified. Thus, AS is not a single-gene disease and the involvement of multiple non-MHC genes may account for the individual as well as geographical differences seen in AS.
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PMID:The genetic background of ankylosing spondylitis. 1954 28

The Spondyloarthritis Research and Therapy Network (SPARTAN), founded in 2003 to promote research, education, and treatment of ankylosing spondylitis (AS) and related forms of spondyloarthritis (SpA), held its 6th Annual Research and Education Meeting in July 2008 in Cleveland, Ohio, USA. The overall theme of the meeting was entheses and bones in SpA, which included presentations on the anatomy and physiology of the synovial-entheseal complex; bone formation and destruction, and the effect of inflammation on bone; the Th17 axis, HLA-B27, IL23R, and ARTS1; and breakout sessions on epidemiology and registries.
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PMID:Entheses and bones in spondyloarthritis: 2008 Annual Research and Education Meeting of the Spondyloarthritis Research and Therapy Network (SPARTAN). 1956 33

Recent studies published on the genetic basis of ankylosing spondylitis (AS) reflect novel areas of investigation and extension of recent advances. As HLA-B27 subtypes have been extensively examined in other ethnic groups, novel insights into the relevance of HLA-B27 folding to disease susceptibility have led to questions regarding the influence of HLA-B27 on AS pathogenesis. The recent identification of IL23R, ERAP1, and interleukin-1 (IL1A) region genes in AS pathogenesis has led to a number of replication studies. Other genes with inconsistent AS associations (eg, KIR, TLR4, ANKH, and TNAP) have been further examined with inconsistent results. Potential candidate genes (TIRAP, COL1A6, and MEFV) have been examined with no associations found. Tremendous progress has been made with respect to understanding the genetic basis of AS. The identification of new genes-ARTS1, IL23R, and IL1A-substantiate that susceptibility to AS is also determined by genes outside the MHC.
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PMID:Recent studies on the genetic basis of ankylosing spondylitis. 1977 29

Endoplasmic reticulum aminopeptidase 1 (ERAP1) and the closely related ERAP2 are involved in the final trimming of peptides within the endoplasmic reticulum for presentation by major histocompatibility complex (MHC) class I molecules. ERAP1 was found to be associated with ankylosing spondylitis (AS) in a genome-wide association study of nonsynonymous single nucleotide polymorphisms, and this association has been confirmed in several studies. An ERAP1/ERAP2 haplotype has also been reported to be associated with familial AS. ERAP1 and ERAP2 could carry out several potential roles in the pathogenesis of AS. ERAP1-deficient mice show a considerable alteration in the level and repertoire of peptides presented by MHC class I molecules. Furthermore, ERAP1 has been shown to be involved in shedding cytokine receptors. Both of these functions require further analysis to better understand the exact role of ERAP1 in AS.
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PMID:Endoplasmic reticulum aminopeptidases: Biology and pathogenic potential. 2053 81

Endoplasmic reticulum aminopeptidase 1 (ERAP1) and interleukin-23 receptor (IL-23R) gene polymorphisms were found to be associated with ankylosing spondylitis (AS) in a nonsynonymous single nucleotide polymorphism association study, and this has been replicated in several studies across different populations. ERAP1 variants could lead to significant changes in the repertoire of peptides presented by MHC-I. Reading this in conjunction with the known association of AS with HLA-B27, a functional interaction between ERAP1 and HLA-B27 is very likely. ERAP1 has additionally been shown to be involved in cytokine receptor shedding. The IL-23R is one of the two receptors that mediate the action of IL-23. AS is associated with the same polymorphisms of IL-23R as those linked to psoriasis and inflammatory bowel disease. This suggests common genetic risks linking AS and extra-articular manifestations. This review focuses on the pathogenic potential of these two genes in AS.
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PMID:Endoplasmic reticulum aminopeptidase 1 and interleukin-23 receptor in ankylosing spondylitis. 2278 41

The strong genetic association of ERAP1 (endoplasmic reticulum aminopeptidase 1) with ankylosing spondylitis (AS), which is restricted to HLA-B27 positive cases, has profound pathogenetic implications. ERAP1 is involved in trimming peptides to optimal length for binding to HLA class 1 molecules, thereby not only affecting the stability and processing of HLA-B27 but also influencing the peptide repertoire presented to the immune system. This could have secondary effects on specific adaptive or autoimmune responses in AS. However, it appears increasingly likely that the pathogenic effect of ERAP1 may be mediated through effects on innate immunity, such as altering the interaction between HLA-B27 and immune receptors such as the killer immunoglobulin-like receptors (KIR) found on a range of innate immune cells or via the endoplasmic reticulum unfolded protein response. ERAP1 variants associated with reduced endopeptidase activity appear to be protective against AS, raising the possibility that ERAP1 inhibition could represent a future treatment strategy.
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PMID:ERAP1 and ankylosing spondylitis. 2345 40

The endoplasmic reticulum aminopeptidase 1 (ERAP1) is a multifunctional enzyme involved in the final processing of Major Histocompatibility Complex class I (MHC-I) ligands and with a significant influence in the stability and immunological properties of MHC-I proteins. ERAP1 polymorphism is associated with ankylosing spondylitis among HLA-B27-positive individuals and the altered enzymatic activity of natural variants has significant effects on the HLA-B27 peptidome, suggesting a critical pathogenetic role of peptides in this disease. Likewise, the association of ERAP1 with other MHC-I associated disorders and its epistasis with their susceptibility MHC alleles point out to a general role of the MHC-I peptidome in these diseases. The functional interaction between ERAP1 and HLA-B27 or other MHC-I molecules may be related to the processing of specific epitopes, or to a more general peptide-dependent influence on other biological features of the MHC-I proteins. In addition, from a consideration of the reported functions of ERAP1, including its involvement in angiogenesis and macrophage activation, a more complex and multi-level influence in the inflammatory and immune pathways operating in these diseases cannot be ruled out.
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PMID:ERAP1 structure, function and pathogenetic role in ankylosing spondylitis and other MHC-associated diseases. 2391 68


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