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)

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

In this review we consider diseases associated with pathological mineralization/ossification, namely, ankylosing spondylitis (AS), osteoarthritis (OA), generalized artery calcification of infancy (GACI), vascular calcification as well as chondrocalcinosis (CC) and pseudo gout. Deciphering the key enzymes implicated in the calcification process is an objective of prime importance and the ultimate goal is to synthesize inhibitors of these enzymes in order to provide efficient alternate therapeutic strategies that will slow down the pathologic mineralization and complement the arsenal of anti-inflammatory drugs. One of the difficulties in the definition of diseases associated with pathologic mineralization/ossification lies in the controversial relationship between the type of calcification and the nature of the disease. Here, we propose to clarify this relationship by making a distinction between diseases associated with hydroxyapatite (HA) and calcium pyrophosphate dihydrate (CPPD) deposits. AS, OA, GACI and vascular calcification are usually characterized by mineralization/ossification associated with HA deposits, while CC and pseudo gout are mostly characterized by CPPD deposits. Although both HA and CPPD deposits may occur concomitantly, as in chronic pyrophosphate arthritis or in OA with CPPD, they are formed as a result of two antagonistic processes indicating that treatment of distinct diseases can be only achieved by disease-specific drug therapies. The hydrolysis of PPi, an inhibitor of HA formation, is mostly controlled by tissue non-specific alkaline phosphatase TNAP, while PPi production in the extracellular medium is controlled by ANK, a PPi transporter, and/or NPP1 which generates PPi from nucleotide triphosphates. Low PPi concentration may lead to a preferential deposition of HA while high PPi concentration will favor the formation of CPPD deposits. Thus, HA and CCPD deposition cannot occur concomitantly because they are determined by the Pi/PPi ratio which, in turn, depends on the relative activities of antagonistic enzymes, TNAP hydrolyzing PPi or ANK and NPP1 producing PPi. TNAP inhibitors could prevent HA formation in AS, in late OA, in GACI, as well as in vascular calcifications, while ANK or NPP1 inhibitors could slow down CCPD deposition in CC and pseudo gout.
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PMID:Ankylosing spondylitis, late osteoarthritis, vascular calcification, chondrocalcinosis and pseudo gout: toward a possible drug therapy. 2151 61

The aim of this study was to investigate two mineralization-related genes TNAP and ANKH polymorphisms associated with ankylosing spondylitis (AS) in the North Chinese Han population. We carried out a case-control study in Chinese AS cohorts involving 278 AS patients and 286 unrelated healthy controls. Five TNAP SNPs (rs3200254, rs1256348, rs1472563, rs1780329, rs3767155) and four ANKH SNPs (rs25957, rs26307, rs27356, rs28006) were genotyped by the Multiplex Snapshot method. There were significant differences in genotype (permutated p = 0.00481) and allele (permutated p = 0.0126) frequencies of the rs26307 ANKH SNP between AS patients and controls. Logistic regression analysis suggested an association of AS with the polymorphism in an additive model (OR = 0.640, 95%CI = 0.480-0.853, p = 0.0023, permutation 10,000 corrected p = 0.0158) and a dominant model (OR = 0.599, 95%CI = 0.423-0.846, p = 0.0037, permutation 10,000 corrected p = 0.022). Haplotype analysis identified the ANKH haplotype rs26307(C)/rs27356 (T) as a predisposing factor for AS (OR = 1.53, 95%CI = 1.165-2.071, p = 0.0026, permutation 10,000 corrected p = 0.0103). This study provides evidence that variation in the ANKH gene influences susceptibility to AS in the Northern Han Chinese population.
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PMID:Association of mineralization-related genes TNAP and ANKH polymorphisms with ankylosing spondylitis in the Chinese Han population. 2361 78