TAP1 and TAP2 Polymorphism in Spanish Patients with Ankylosing Spondylitis

Fraile, Aurora; Collado, María; Matarán, L.; Martı́n, Javier; Nieto, Antonio

doi:10.1159/000019139

Cited by 23 publications

(14 citation statements)

References 22 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…HLA-B27, which is encoded in the class I major histocompatibility complex (MHC) region, confers the greatest known susceptibility to AS, and up to 95% of patients of European ancestry are HLA-B27 positive (1,5). In addition to HLA-B27, other MHC genes have also been implicated in AS, including HLA-DRB1 (6), tumor necrosis factor ␣ (TNF␣) (1), transporter-associated protein 1 (7), and low molecular weight protein 1 (8).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Genetic studies in familial ankylosing spondylitis susceptibility

Zhang¹,

Luo²,

Brückel³

et al. 2004

Arthritis & Rheumatism

104

View full text Add to dashboard Cite

Objective. To define the genetic basis of susceptibility to ankylosing spondylitis (AS), especially nonmajor histocompatibility complex (MHC) genes.Methods. The study group comprised 244 affected sibling pairs from 180 pedigrees of primarily European ancestry. Sibling pairs were concordant for AS by the modified New York criteria and had available sacroiliac radiographs. The subjects were genotyped for 400 markers in ABI PRISM linkage map MD-10 and for 17 additional markers on chromosomes 6p, 6q, and 11q (including HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles). Two-point and multipoint nonparametric linkage (NPL) analyses were conducted using the NPL statistic and 1-parameter allele-sharing model logarithm of odds (LOD) scores, calculated using the AlleleSharing Model (ASM) computer program.Results. Linkage of the MHC region was supported by both 2-point and multipoint analyses, with the strongest peak (45.90 cM) in the MHC at the HLA-DRB1 locus (NPL score 8.720, ASM LOD score 20.49; P ‫؍‬ 6.8 ؋ 10 ؊20 for 2-point analysis). A second region was found to have positive linkage at the q arm of chromosome 6 (D6S441) in 2-point analysis; this was supported by a 39.13-cM region (135.58-174.71 cM) in multipoint analysis, with the smallest P value (4.2 ؋ 10 ؊3 ) at 166.39 cM. A third region was found on chromosome 11q, with the strongest evidence for linkage for D11S4094 at 123 cM (NPL score 2.235, ASM LOD score 1.939) and, on transmission disequilibrium test analysis, D11S4090 at 105.74 cM (P ‫؍‬ 6.2 ؋ 10 ؊5 ). Linkage in this area was supported by multipoint analysis, spanning 22.19 cM continuously from 101.68 cM to 123.87 cM, with the strongest peak at 112.33 cM (P ‫؍‬ 0.014); this was confirmed by subsequent fine mapping studies.Conclusion. Thus, this genome-wide scan implicates, in addition to the MHC, regions outside the MHC in AS susceptibility, especially on chromosomes 6q and 11q.Ankylosing spondylitis (AS) is a common chronic inflammatory disorder primarily affecting the spine, although the peripheral joints and the attachments of ligaments and tendons to joints (the entheses) are also frequently involved, as well as the eyes, and, less com-

show abstract

mentioning

confidence: 99%

“…Although the MHC is likely the primary mediator of genetic susceptibility to AS, it explains Ͻ50% of the total genetic risk for AS (6,7). Genome-wide linkage scans have implicated numerous non-MHC genomic regions, including 1p, 2p, 2q, 3p, 9q, 10q, 11p, 19q, and 16q (9,10).…”

mentioning

confidence: 99%

Genetic studies in familial ankylosing spondylitis susceptibility

Zhang¹,

Luo²,

Brückel³

et al. 2004

Arthritis & Rheumatism

104

View full text Add to dashboard Cite

show abstract

“…Whether the polymorphism has any functional significance remains unknown. TAP1 and TAP2 polymorphisms in AS patients and controls were compared; no significant differences in the genotype distribution were found [68]. The frequency of the TAP1B allele was greater in patients with AS than in random controls, but linkage disequilibrium with HLA-B27 could not be ruled out.…”

Section: Mhc Genesmentioning

confidence: 92%

Predisposing factors in the Spondyloarthropathies: New insights into the role of HLA-B27

Colbert

Prahalad

2001

Curr Rheumatol Rep

View full text Add to dashboard Cite

Spondyloarthropathies represent complex genetic diseases whose development is influenced by environmental factors. Estimates suggest that three to nine loci may be responsible for the majority of the genetic susceptibility to ankylosing spondylitis. The only susceptibility locus identified to date in multiple populations is HLA-B, where several HLA-B27 alleles (subtypes) are strongly associated with disease. Recent evidence implicates cytochrome P450 2D6 as a second locus, although its influence on overall risk appears small. Despite considerable efforts to define how HLA-B27 contributes to disease, its role remains enigmatic. Increasing evidence suggests it has effects that are unrelated to its physiologic function. The basis for this is unknown but may be a consequence of the unusual tendency of this allele to misfold.

show abstract

“…The entire effect of the major histocompatibility complex (MHC), however, is approximately 50%. Other MHC genes also have been implicated in AS in addition to B27, including HLA-DRB1 [26,27], MHC class I chain-related protein A [28], TNF-α [29,30], heat shock protein 70 [31], transporter associated with antigen processing-1 [32], and latent membrane protein-2 [33]. Psoriasis per se has been associated with HLA-B13, B37, and B57, which are linked to HLA-Cw6 (C*0602) [34].…”

Section: Other Major Histocompatibility Genesmentioning

confidence: 99%

The genetic basis of spondyloarthritis

Reveille

2004

Curr Rheumatol Rep

View full text Add to dashboard Cite

Spondyloarthritis tends to cluster in families and, to a great extent, is associated with human leukocyte antigen (HLA) B27. In fact, the population frequency of spondyloarthritis in most groups is proportional to that of HLA-B27. But the frequency of HLA-B27 in the population-at-large far exceeds that of spondyloarthritis, suggesting other genetic factors also are operative. Other major histocompatibility complex genes have been implicated, especially HLA-DR, though linkage to HLA-B27 confounds the analysis of this in many studies. Genome-wide scans have implicated regions on chromosomes 2q, 6p, 6q, 10q, 11q, 16q, 17q, and 19q in ankylosing spondylitis, on 4, 6p, and 17q in psoriasis, and on 7q and 16q in inflammatory bowel disease. The search for non-major histocompatibility complex candidate genes has been complicated by inadequate power, because of the small effect they exert on overall disease susceptibility, although recent studies are revealing promising candidates that must be confirmed by other groups.

show abstract

TAP1 and TAP2 Polymorphism in Spanish Patients with Ankylosing Spondylitis

Cited by 23 publications

References 22 publications

Genetic studies in familial ankylosing spondylitis susceptibility

Genetic studies in familial ankylosing spondylitis susceptibility

Predisposing factors in the Spondyloarthropathies: New insights into the role of HLA-B27

The genetic basis of spondyloarthritis

Contact Info

Product

Resources

About