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)

The system was designed with emphasis on the identification HLA-B alleles and genotypes associated or potentially associated with seronegative arthritides. By using a combination of multiplex SSP and PCR-RFLPs, the assays can be economically performed on a large range of sample sizes in diagnosis and epidemiology. 24 HLA-B alleles and subtypes can be discriminated, including options for PCR-RFLP or sequence specific amplification of the allele groups B27 and B60 (B*4001 and B*4007). In addition, the internal control carries central MHC polymorphisms, which can help to identify HLA extended halplotypes. False negatives, caused by preferential amplification of the internal control under suboptimal PCR conditions, were prevented by employing new, optimized PCR buffer. Four of the HLA-B primers were pooled into a multiplex reaction whose products were subtyped by digestion with seven restriction endonucleases. Specificity and sensitivity were verified in a panel of 68 homozygous cell lines and 200 heterozygous samples. An HLA-B*27-B*40 hybrid allele was observed in 3 out of 95 B*27-positive individuals from Berlin, Germany. Such an allele could be mistyped by some published assays as a B*27/B*40 heterozygote, a genotype reported to confer an increased risk for ankylosing spondylitis.
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PMID:An integrated multiplex-PCR and PCR-RFLP typing system for markers associated with seronegative arthritides. 953 35

Despite the strength of the association of ankylosing spondylitis (AS) with HLA-B27, other genetic elements could play a possible role in the pathophysiology of AS. Because of the localization, in the proximity of the HLA-B locus, and the involvement of heat shock proteins (HSP) in the immune response, we analyzed the influence of HSP70 gene polymorphism on the susceptibility to AS. HSP70-1, HSP70-2 and HSP70-hom genotypes were analyzed by PCR-RFLP in patients with AS and in healthy controls. The results obtained in the present study showed that there are not significant differences in the distribution of HSP70-hom genotypes, whereas significant differences in HSP70-1 and HSP70-2 genotypes between AS patients and random controls were found. However, when the distribution of these genotypes were compared in B*27-matched AS patients and controls, the differences disappeared. These data suggest that the polymorphism of HSP70 genes was not independently associated with AS, and that the differences in HSP70-1 and HSP70-2 genotypes among AS patients and controls appears to be due to the linkage disequilibrium between HSP70 alleles and HLA-B*27.
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PMID:HSP70 gene polymorphisms in ankylosing spondylitis. 958 10

Despite the strength of the association of ankylosing spondylitis (AS) with HLA-B27, other genetic elements could play a possible role in the pathophysiology of AS. In view of its gene location, in the proximity of the HLA-B locus, and biological effects, tumor necrosis factor (TNF) genes are potential candidates for additive susceptibility factors to AS. TNFalpha and TNFbeta genotypes were analyzed by PCR-RFLP in 57 patients with AS, 102 random controls and 30 HLA-B*27-positive controls. No significant differences of TNFalpha promoter variations at position -308 and -238 were found in AS patients in comparison with controls. The -244 polymorphism was not detected in our population. The TNFbeta genotype frequency was significantly different between AS patients and random controls. However, when the distribution of the TNFbeta genotype was compared in B*27-positive AS patients and controls, these differences disappeared. In addition, we demonstrated that the TNFbeta*1 was in strong linkage disequilibrium with the B*27 allele, which may explain the differences observed for the TNFbeta genotype among AS patients and random controls. Our data suggest that the polymorphisms of TNFalpha and TNFbeta genes do not have an independent effect on AS susceptibility.
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PMID:Tumor necrosis factor gene polymorphisms in ankylosing spondylitis. 958 11

The HLA-B*27 group of alleles has been extensively studied due to the association of particular B*27 alleles with ankylosing spondylitis (AS). We describe here an HLA-B*27 allele (B*2712) encoding an antigen that lacks reactivity with B27 monoclonal antibodies (moabs) and alloantisera but reacts with some B40/B60 moabs and alloantisera and expresses the Bw6 public epitope. This allele was discovered by the segregation of an HLA-B allele undetectable by PCR-SSP within a Caucasian family from the British population referred for routine bone marrow transplant HLA typing and found in the haplotype A*29; B*2712; Cw*1203; DRB1*13; DQB1*0603. Serological typing showed a lack of reactivity with four B27 moabs and four alloantisera but positive reactivity with moabs and alloantisera specific for B40/B60 and Bw6 public epitopes. Subsequent sequencing showed the closest homology was with B*2708 with three mismatches in exon 2 at positions 204, 209 and 210. The intron 2 sequence was identical with other B*27 lineage alleles including a 2 base pair deletion at positions 95 and 96. The relationship between HLA-B*2712 and reported B60 associations with susceptibility to AS remains to be determined.
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PMID:Functional characterization and exon 2-intron 2-exon 3 gene sequence of HLA-B*2712 as found in a British family. 994 44

HLA-B27 appears to play a direct role in the pathogenesis of ankylosing spondylitis and almost all patients with this disease have HLA-B27. Therefore, a diagnosis of ankylosing spondylitis can virtually be excluded in the absence of HLA-B27. Many techniques have been used for HLA-B*27 typing. Of these, molecular methods are the most sensitive and specific but require extracted DNA as the testing material. A technique where HLA-B*27 is amplified directly from whole blood using sequence specific primers has been developed. This technique uses small sample volumes, is not restricted by choice of anticoagulant or sample age up to at least six weeks, and can be applied to other clinical polymerase chain reaction based procedures.
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PMID:HLA-B*27 typing by sequence specific amplification without DNA extraction. 1074 81

Eighteen different HLA-B*27 alleles (B*2701-B2718) have so far been recognized by the WHO Nomenclature Committee for Factors of the HLA System. Frequency and disease association of these alleles with spondyloarthropathies differ among ethnic groups. We describe here a novel HLA-B*27 subtype identified in a Lebanese patient suffering from ankylosing spondylitis (AS). This new variant differs from the common HLA-B*2705 DNA sequence at five different nucleotide positions. These nucleotide changes lead to three amino acid differences in the alpha2 domain; Thr to Ile at position 94, Leu to Ile at position 95 and Asn to Arg at position 97. Since this novel allele is encountered in an AS patient, the associated sequence changes are not expected to affect significantly neither the presentation of a putative arthritogenic peptide nor the conformation-dependent recognition by effector cells.
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PMID:A new HLA-B*27 allele (B*2719) identified in a Lebanese patient affected with ankylosing spondylitis. 1158 Aug 53

HLA-B*27 is known to be associated with ankylosing spondylitis and several methods have been applied to determine its presence or absence. In this report two molecular methods were used for detection of B*27. The polymerase chain reaction sequence-specific primer (PCR-SSP) method was performed to detect the presence or absence of B*27, whereas the sequence-based typing method (SBT) was used to identify the B*27 subtype. The PCR-SSP method used to detect B*27 was updated to enable the detection of all B*27 alleles. The typing results obtained by this method were compared with the serological typings of 262 individuals. Fifty of them were found to be B*27 positive by PCR-SSP and 46 also showed positive serological reactions with B27-specific sera. The four discrepancies were the result of the presence of B*2712 in three individuals and B*2715 in one individual; both alleles showed no serological reactions with B27-specific antisera. With SBT the sequences of exons 1 through 4 were determined to unequivocally assign the B*27 alleles. Eleven different subtypes were detected in 78 individuals, including three new B*27 alleles: B*27054, B*2715 and B*2717. The allele B*27054 showed an allelic drop out when exon 3 was amplified. Three differences with B*27052 were demonstrated; one in exon 1, one in intron 1 and one in intron 2, the latter being responsible for the allelic drop out. The B*2715 allele was serologically not detectable with several B27-specific sera, but showed Bw4-positive reactions. The sequence of B*2715 showed two mismatches with B*2704. The sequence of B*2717 showed one mismatch with B*27052 at position 248 (A-->T), which was considered to be a conserved position in all B alleles.
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PMID:B*27 in molecular diagnostics: impact of new alleles and polymorphism outside exons 2 and 3. 1236 80

The aim of the present study was to analyze haplotypic associations of two the most common HLA-B*27 subtypes (B*2702 and *2705) in the Croatian population. One hundred and eleven unrelated HLA-B*27 positive individuals were included. None of them had any sign of ankylosing spondylitis. The total number of analyzed haplotypic associations was 112 because one individual was homozygous for HLA-B*27. HLA-B*27 alleles as well as HLA-A and DRB1 specificities were tested by PCR-SSP method. Among seven different HLA-B*27 alleles observed among our individuals, B*2705 was the most frequent (61.6%), followed by B*2702 (30.4%), while the frequency of all other observed alleles (B*2701, B*2703, B*2704, B*2708 and B*2714) was less than 2.0%. HLA-A*02 was the most frequent specificity at HLA-A locus in both groups of haplotypic associations (B*2702 and B*2705) and no difference in distribution of HLA-A genes was observed between two groups. Analysis of HLA-B*2702 haplotypic associations showed the high frequency of DRB1*16 (44.2%) in comparison to B*2705 haplotypic associations (4.0%) with significant P value (P<0.00001). HLA-DRB1*01 demonstrated significantly higher presence among 69 B*2705 haplotypic associations compared to 34 B*2702 haplotypic associations (28.0% vs. 1.5%; P<0.00001).
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PMID:[Haplotipic associations of the two most common HLA-B*27 alleles in the Croatian population]. 1902 62

The HLA region encodes several molecules that play key roles in the immune system. Strong association between the HLA region and autoimmune disease (AID) has been established for over fifty years. Association of components of the HLA class II encoded HLA-DRB1-DQA1-DQB1 haplotype has been detected with several AIDs, including rheumatoid arthritis, type 1 diabetes and Graves' disease. Molecules encoded by this region play a key role in exogenous antigen presentation to CD4+ Th cells, indicating the importance of this pathway in AID initiation and progression. Although other components of the HLA class I and III regions have also been investigated for association with AID, apart from the association of HLA-B*27 with ankylosing spondylitis, it has been difficult to determine additional susceptibility loci independent of the strong linkage disequilibrium (LD) with the HLA class II genes. Recent advances in the statistical analysis of LD and the recruitment of large AID datasets have allowed investigation of the HLA class I and III regions to be re-visited. Association of the HLA class I region, independent of known HLA class II effects, has now been detected for several AIDs, including strong association of HLA-B with type 1 diabetes and HLA-C with multiple sclerosis and Graves' disease. These results provide further evidence of a possible role for bacterial or viral infection and CD8+ T cells in AID onset. The advances being made in determining the primary associations within the HLA region and AIDs will not only increase our understanding of the mechanisms behind disease pathogenesis but may also aid in the development of novel therapeutic targets in the future.
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PMID:The HLA Region and Autoimmune Disease: Associations and Mechanisms of Action. 1941 18

Human leukocyte antigens (HLA), class I, are a group of antigens expressed on most nucleated cell surfaces. They transport endogenous peptides to the cell surface for recognition by T-cell receptors. Their functions are involved in immune responses. Many diseases are associated with HLA alleles, especially HLA-B*27 that is strongly associated with ankylosing spondylitis (AS). HLA-B*27 consists of 42 subtypes. Different subtypes of HLA-B*27 were reported in different ethnic groups of AS patients. In this study, a high-resolution polymerase chain reaction-sequence-specific primer technique has been developed to define all the HLA-B*27 subtypes with a total of 29 primer mixtures. Two of the primer mixes were used to detect the HLA-B*27-specific group, and 27 primer mixes were used to identify 42 subtypes (B*2701-B*2721 and B*2723-B*2743). The HLA-B*27-group-specific primers have been tested in unrelated healthy subjects; 846 Northeastern Thais (NET), 334 Northern Thais (NT), 264 Karens, and 310 Bamars. Sixty-three NET (phenotype frequency, PF = 7.4%), 24 NT (PF = 7.1%), 5 Karens (PF = 1.8%), and 12 Bamars (PF = 3.9%) were positive for HLA-B*27. Only B*2704 was found in Karens, whereas B*2704, B*2705/37/39, B*2706, and B*2707 were found in NET and NT. In Bamars, B*2704, B*2705/37/39, B*2706, and B*2725 were found. The distribution of HLA-B*27 subtypes was compared with other studies in Asian and Caucasian populations. Significant differences of the distribution of HLA-B*27 subtypes were found in most of the populations. This study established a simple technology for HLA-B*27 subtyping and provided basic information for anthropology and further studies in disease associations.
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PMID:HLA-B*27 subtypes in Northern and Northeastern Thais, Karens, and Bamars determined by a high-resolution PCR-SSP technique. 1949 37


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