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 examined the distribution of non-B27 alleles of the HLA-B locus among B27+ patients with ankylosing spondylitis (AS), to detect any additional HLA-B locus allele(s) that may act in conjunction with B27 to increase susceptibility to AS. HLA-Bw60 (or B40 when the Bw60,61 split of B40 was not typed for) was shown to be increased among B27+ AS patients in each of 5 independent data sets. This increase was statistically significant in 4 of the 5 data sets studied, and the overall significance was P less than 0.00001. Susceptibility to AS in B27+ individuals was further increased by a factor of approximately 3 when Bw60 was also present. The distribution of HLA-A alleles on the B27-bearing haplotypes in AS patients was not significantly different from that in normal controls. On the other hand, the distribution of HLA-A alleles on Bw60-bearing haplotypes was significantly different from the distribution of A alleles on Bw60 haplotypes in the general population (P less than 0.0005). Bw60 was not increased in B27- patients with AS. A dominant mode of inheritance generally fits AS; however, our sib pair analysis indicates that the B27,Bw60 disease subgroup follows a more recessive mode of inheritance.
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PMID:HLA-Bw60 increases susceptibility to ankylosing spondylitis in HLA-B27+ patients. 199 28

Genomic DNA from 46 B27+ ankylosing spondylitis, Reiter's syndrome, or normal individuals was digested with Taq I and probed, in Southern blots, with the HLA-B locus specific probe, EI7. Four restriction fragment length polymorphisms (RFLP), 2.5, 3.4, 3.8 and 4.0 or 8.0 kb, were observed for the B27 gene. In Caucasians, one of the B27 variants (2.5 kb) was more frequent in normals and almost never appeared in patients, suggesting a trend that is not yet statistically significant. In the course of defining the B27 polymorphisms, three and two RFLP, respectively, were also found for the B18 and B44 genes.
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PMID:New polymorphisms of HLA-B27 and other B locus antigens detected by RFLP using a locus-specific probe. 287 15

A 3.5-kb HLA class I fragment is polymorphic in an ankylosing spondylitis (AS) family. All B27 AS patients show the 3.5-kb band, which is also present in B12 AS patients in this family. When hybridized with an HLA-B-specific probe, the polymorphic band is revealed in B12 patients, but not in B27 patients.
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PMID:Taq I polymorphism of HLA class I genes in an ankylosing spondylitis family. 290 13

A 435-kilobase (kb) DNA segment, which is centromeric to HLA-B in the human major histocompatibility complex, was isolated by chromosome walking with overlapping cosmids. Within the cloned region, the genes for the tumor necrosis factors (TNFs) alpha and beta and HLA-B were 210 kb apart. The human homolog of a mouse gene, B144, was located next to TNF alpha. Moreover, the presence of additional genes was suggested by a large cluster of CpG islands. With cosmid probes, several distinct transcripts were detected in RNA samples from a variety of cell lines. Altogether, five novel genes were identified by isolation of corresponding complementary DNA clones. These "HLA-B-associated transcripts" (BATs) were mapped to different locations within a 160-kb region that includes the genes for TNF alpha and TNF beta. The presence of the genes for BAT1 and BAT5 in the vicinity of HLA-B again raises the question of which gene in this region determines susceptibility to ankylosing spondylitis.
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PMID:A new cluster of genes within the human major histocompatibility complex. 291 34

Ninety percent of individuals with ankylosing spondylitis (AS) express HLA-B27. To determine if HLA-B27 coding sequences from normal vs AS individuals show differences that might relate to the etiology of the disease, the gene coding for this allele was cloned from three different partial genomic libraries. These libraries were made with DNA from three different cell lines expressing HLA-B27: MRWC (HLA-B27, 14), obtained from an AS patient; KCA (HLA-B27, w44), obtained from a known normal individual; and MVL (HLA-B27, 27), a homozygous consanguineous cell line of unknown origin. To increase the number of clones coding for the HLA-B locus, partial libraries were made using a complete Eco RI digestion of genomic DNA in the lambda vector 607. The libraries were screened with two probes; one probe hybridizes to all HLA-A, B, C class I genes, and the other to a small subpopulation of class I genes, including the B locus. DNA from clones hybridizing with both probes was transfected into murine L cells. Cell surface expression of HLA-B27 on murine L cells was detected with a polymorphic monoclonal antibody (ME1) specific for HLA-B27, 7, 22. DNA from those clones positive for HLA-B27 by transfection was subcloned into the Xba I site of M13mp18 and the DNA sequence for exons 2 through 4 (encoding domains alpha 1, alpha 2, and alpha 3) was determined by the dideoxy technique by using synthetic oligonucleotide primers or the M13 primer. The resulting sequences show no difference between HLA-B27 alpha 1, alpha 2, alpha 3 domains from a known AS patient and a known normal individual.
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PMID:Absence of polymorphism between HLA-B27 genomic exon sequences isolated from normal donors and ankylosing spondylitis patients. 348 55

15 east Austrian patients (EUC) with HLA-B27-negative ankylosing spondylitis (AS) were tissue-typed for HLA-B-antigens. HLA-B-alleles of the B27-CREG (B7, B13, Bw22, B40) were found in 14/15 patients (= 93,3%; RR = 37,8; Chi2 = 23,21; p less than 0.05) of this group. We may postulate a common partial-antigen for AS, carried by HLA-alleles belonging to the B27-CREG. This partial-antigen may either react in a direct pathway with the unknown pathogenic agent of AS or represent a marker for the "disease-susceptibility genes" of AS.
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PMID:[Cross-reacting HLA-B alleles as genetic markers of HLA-B27 negative ankylosing spondylitis]. 349 38

67 patients with ankylosing spondylitis (AS) were tissue-typed for HLA-A, -B and -C antigens. HLA-Bw62 was found in 6 of 13 (46%) HLA-B27 negative patients, compared to 9% in HLA-B27 positive AS (p greater than 0.01) and 10% in healthy blood donors (p greater than 0.001). HLA-Bw62, a split of the previous HLA-B15, belongs to the HLA-Bw35 CREG antigens, 11 of 13 (85%) of HLA-B27 negative patients had an HLA-Bw35 CREG antigen. The present results are interpreted as an indication of a direct involvement of the HLA-B locus in the pathogenesis of AS.
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PMID:Increased frequency of HLA-Bw62 and Bw35 CREG antigens in HLA-B27 negative ankylosing spondylitis. 633 28

Although HLA-B27 carries a high relative risk for development of ankylosing spondylitis (AS), most B27 positive individuals do not have spondylitis. One interpretation of this observation is that there may be 2 types of B27, 1 which carries the risk factor and 1 which does not. If this were the case, then with the help of markers closely linked to HLA-B, it might be possible to detect differences between the B27 haplotypes in AS patients and those in healthy probands. We studied 197 members of 18 families with known AS and 110 members of 19 families in which HLA-B27 was present without any known inflammatory spinal disease. HLA antigens A, B, and C and alleles of complement components C2, C4, and Factor B and glyoxalase-1 were determined in all cases. Detailed haplotypes were assigned and their associations with development of the disease were examined. We were unable to identify any distinct HLA-B27 haplotype associated with AS; 2 common haplotypes and several miscellaneous ones were found in both groups. Thinking that the development of AS might be influenced by the other, non-B27 haplotype, we analyzed this and found that there was no detectable influence. The data do not contradict the notion that B27 in whites is a single entity and is itself the susceptibility factor predisposing to the development of ankylosing spondylitis.
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PMID:HLA-B27 haplotypes in family studies of ankylosing spondylitis. 660 47

The authors have provided a new recurrence risk table of ankylosing spondylitis. The mathematical problem solved was to combine a continuous distribution for polygenic inheritance with a discrete one, HLA-B-27 antigen 'yes' or 'no'. Previously the highest probability of recurrence was 0.0785 in the case of an affected mother's son and it increased to 0.1416 when the B-27 antigen positive affected mother had a B-27 positive son.
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PMID:Calculation of recurrence risk in the case of ankylosing spondylitis taking into consideration the antigen HLA-B-27. 660 13

Thirteen families were studied for the frequency of HLA-B27 and allotypes of the components of complement, C2, C4 and Bf. The 13 probands all suffered from definite ankylosing spondylitis (AS) as defined by the New York criteria. The results showed that HLA-B27 positive haplotypes in AS patients possessed different complement allotypes. Thus, it is postulated that the gene conferring predisposition to the development of AS is either HLA-B27 itself or another gene in very close proximity to the HLA-B locus.
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PMID:HLA-B27 and allotypes of complement components in ankylosing spondylitis. 661 Jul 55


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