Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003873 (rheumatoid arthritis)
 53,068 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A major component of genetic susceptibility to rheumatoid arthritis (RA) appears to be explained by inheritance of HLA-DRB1 alleles, which have a conserved sequence of amino acids in the third hyper-variable region of the molecule. This "shared epitope" is found on various DR4, DR1, and DR6 variants, as well as on DR10. The evidence for this "shared epitope" in RA is examined at the population level, including how it fits in with the available epidemiologic data and RA disease severity.
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PMID:Population genetics of rheumatoid arthritis. 128 Aug 45

Rheumatoid arthritis (RA) is primarily associated with HLA-DR4 in a wide range of ethnic groups. DNA analysis of HLA-DRB1 sequences shows that a limited set of alleles are positively associated with the disease. Third hypervariable region sequences QRRAA, QKRAA and RRRAA are found in up to 85% of RA patients and may constitute the basic unit of association. Risk estimates for alleles and hypervariable regions differ between ethnic groups and subsets of patients. Severe RA and Felty's syndrome are significantly associated with DR4 Dw4 and, to a lesser extent, with DR4 Dw14. In patients the latter allele is almost exclusively found in combination with Dw4, suggesting that complementation is occurring. Critical substitutions in the peptide binding groove correlate with the presence of RA, suggesting that the disease may be driven by the presentation of specifically bound peptide and/or may be influenced by differential selection of the T cell repertoire.
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PMID:The HLA association with rheumatoid arthritis. 158 78

Extensive studies in different ethnic groups have associated the susceptibility to development of rheumatoid arthritis (RA) with the third hypervariable region of the major histocompatibility complex (MHC) HLA-DR beta 1 molecule. On the basis of recent findings in the experimental mouse model of collagen-induced arthritis, Eric Zanelli, Miguel Gonzalez-Gay and Chella David propose that the HLA-DRB1 locus is associated with protection to RA and that the actual arthritogenic peptide-presenting molecule is HLA-DQ. Thus, the development of RA would depend upon the expression of the susceptible DQ allele and the nonprotective DRB1 alleles, along with environmental factors that trigger the autoimmune process.
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PMID:Could HLA-DRB1 be the protective locus in rheumatoid arthritis? 754 77

Rheumatoid arthritis (RA) is likely the result of a concerted action of several inherited and noninherited factors. Although there is a high suspicion that environmental factors are important, proof is missing. Most information has been collected on genetic risk factors. The inheritance pattern for RA is complex, and there is good evidence that HLA as well as non-HLA genes are involved. Almost all racial-ethnic groups share the association of RA with the HLA-DRB1-encoded sequence motif QKRAA or QRRAA. However, the completeness of the association varies significantly in different ethnic cohorts, as can be expected in a multigene model. The sequence motif translates into a pocket in the antigen-binding site of the HLA-DR molecule. The "rheumatoid pocket" accommodates peptide side chains and has distinct binding characteristics. Epidemiologic evidence points toward a role for non-HLA genes. Candidate genes, such as transporter in antigen processing (TAP) genes are currently explored. Major advances in defining and understanding the contribution of inherited and noninherited factors in RA may come from abandoning the concept of RA as a single entity and accepting a heterogeneity model for RA. Distributions of HLA-DR genes indicate that several subsets of RA patients exist. Seronegative (prognostically good) and seropositive (prognostically worse) patients can be distinguished by the arginine versus lysine substitution at position 71 of the HLA-DRB1 gene. A different dimension of disease, rheumatoid organ disease, appears to be reached in patients with two HLA-DRB1*0401 alleles. Identification of distinct RA subsets may allow us to stratify patients into categories that differ with respect to etiology, disease course, clinical pattern, and treatment response.
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PMID:Inherited and noninherited risk factors in rheumatoid arthritis. 761 12

To identify genes that contribute to the manifestation of rheumatoid arthritis we performed association studies via microsatellite analyses of immunorelevant loci (HLA-DRB, 5 T cell receptor loci, TNFa IL1, IL2, IL5R and CD40L). A total of 183 patients and 275 healthy controls were typed in terms of HLA and grouped according to the known predisposing HLA-DRB1 genes (DRB1*04; relative risk approx. 5; DRB1*01, relative risk approx. 2; a third group carried neither allele). Microsatellite polymorphisms characterizing the TCRBV6S3, CD3D, IL1A, IL2, and IL5R genes did not show significant associations with rheumatoid arthritis, whereas TCRBV6S1, TCRBV6S7, TNFa, and CD40L genes may influence relative protection or risk in certain groups of patients. Analysis of a microsatellite marker adjacent to the transcription element alpha (TEA) in the T cell receptor alpha delta complex indicates that in the cohort carrying neither the DRB1*04 nor the DRB1*01 allele the relative risk to acquire rheumatoid arthritis is increased (> 13) or decreased (< 0.07), depending on the inherited microsatellite allele adjacent to the TEA locus. Sequence analysis of the closely linked TEA region from patients and controls revealed a novel dimorphism. Only the newly identified TEA allele leads to binding of a nuclear protein that may be involved in the regulated expression of the TCRDA genes. Subsequent typing of rheumatoid arthritis patients and controls revealed, however, that the association of the microsatellite marker is largely independent of the TEA allele, confirming incomplete linkage in the 2 kb region of the TCRDA locus. These results are discussed in the context of hot spots of recombination in this genomic region and other linked candidate sequences that predispose to develop rheumatoid arthritis.
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PMID:Immunoprinting: various genes are associated with increased risk to develop rheumatoid arthritis in different groups of adult patients. 763 38

Rheumatoid arthritis is a frequently and potentially severe disease which causes a functional handicap in nearly half the patients 10 years after the identification of the first clinical manifestations. Some patients develop very severe forms with joint destruction and multiple organ involvement while in others the disease remains benign, even after a long clinical course of several years. Theoretically, the future intensity of rheumatoid arthritis in a given patient cannot be predicted at the time of early diagnosis. No prognosis factor has been identified and universally accepted and validated. A marker of prognosis would be highly appreciated by clinicians who could then more closely adapt their management decisions to the disease potential. Clinical and biological data collected to date have provided a limited amount of prognostic information but recent progress in molecular biology suggests that genetic markers could be correlated with disease severity. Several HLA-DRB1 alleles including DR1*0401, DRB1*0404, DRB1*0101 and sometimes DRB1/1001 and DRB1/1402 are potential markers. In France 85% of the patients with rheumatoid arthritis have one of these genes compared with 25% in the general population. In patients with a "high risk" alleles, the second haplotype could also have prognostic value. It would appear possible to distinguish immunogenetically homogeneous subpopulations corresponding to the more severe forms of the disease. It is still too early to propose therapeutic strategies based on current prognosis markers, but a combination of the most pertinent markers should be already used to select homogeneous subsets of patients in fundamental research and clinical trials.
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PMID:[Can the prognosis of early rheumatoid arthritis be predicted?]. 763 13

The association of rheumatoid arthritis (RA) with HLA-DRB1 alleles indicates that at least one RA susceptibility gene is linked to the HLA class II region. Transporter associated with protein processing (TAP) genes, which lie upstream of the HLA-structural genes, may also contribute to disease susceptibility. We investigated polymorphisms of the peptide transporter genes, TAP 1 and TAP 2, by PCR-ASO hybridization techniques in 82 RA patients and 66 control individuals. Although there was a suggestion of linkage between some TAP polymorphisms and RA, these seem to be dependent on HLA-DRB1*04, since these positive associations disappeared when HLA-DRB1*04 positive RA patients and controls were compared. Furthermore, no particular TAP allele or haplotype was associated with any clinical or immunological subgroup of RA. We conclude that the TAP genes do not have a major influence on susceptibility to RA in the European Caucasian population.
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PMID:Peptide transporter genes (TAP) polymorphisms and genetic susceptibility to rheumatoid arthritis. 772 93

The contributions of germline-encoded T cell receptor segments and of HLA-DR polymorphisms in shaping the repertoire of human CD4+ CD45RO- T cells were investigated in healthy unrelated individuals and in patients with rheumatoid arthritis, an HLA-DRB1 04-associated disease. By comparing frequencies of V beta-J beta combinations, healthy individuals segregated into independent clusters, which strongly correlated with the HLA-DRB1 allele expression. The repertoire fingerprint imposed by the HLA-DRB1 alleles involved only a selected group of J beta elements, whereas the distribution of the other J beta segments was HLA independent. The HLA-restricted J beta elements are characterized by a Gly-Pro-Gly sequence within the conserved Phe-Gly-X-Gly motif, which induces rigidity in an otherwise more flexible protein backbone. The T cell receptor repertoire distinguished patients with RA from healthy HLA-DR-matched individuals, suggesting that patients share a selection mechanism that significantly distorts the composition of the T cell receptor repertoire.
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PMID:Mechanisms underlying the formation of the T cell receptor repertoire in rheumatoid arthritis. 779 93

To determine the HLA-DRB1 04 and HLA-DQB1 03 variants associated with rheumatoid arthritis (RA) among Russians who live in West Siberia, we studied patients with RA using the polymerase chain reaction and dot-blot hybridization with oligonucleotide probes. A significant increase was seen only for DRB1 0404/08, although the predominant variant in DR4+ RA patients was DRB1 0401. We found no significant difference in the DQB1 03 variants in RA cases when compared with controls. The results suggest that in the Russian-Siberian population RA is primarily associated with several DRB1 04 variants that share sequence identity in the third hypervariable region.
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PMID:Oligonucleotide genotyping of HLA-DRB1 04 and HLA-DQB1 03 among Russians in west Siberia suffering from rheumatoid arthritis. 785 64

Sixty-four patients with Takayasu arteritis, 204 patients with rheumatoid arthritis (RA), 53 patients with systemic lupus erythematosus (SLE) and 64 patients with mixed connective tissue disease (MCTD) in the Japanese population were typed for HLA class II genes at DNA level. The results suggest that susceptibility to Takayasu arteritis is controlled by HLA-B52-DRB1*1502-DRB5*0102-DQA1*0103-DQB1 *0601-DPA1*02-DPB1*0401 haplotype, because the frequency of that HLA haplotype was increased with statistical significance in the patients as compared with that in the healthy controls. On the other hand, the HLA-DRB1*0405-DQA1*0301-DQB1*0401 haplotype was associated with the susceptibility to RA. Susceptibility to SLE and MCTD are controlled by the HLA-DRB1 *1501-DRB5*0101-DQA1*0102-DQB1*0602 haplotype and the HLA-DRB1*0401-DRB4*0101- DQA1*0301-DQB1*0301, haplotype respectively. These observations clearly indicate the presence of HLA-linked disease susceptibility genes to Takayasu arteritis, RA, SLE and MCTD, and the difference in HLA-linked genetic background between these four diseases.
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PMID:[HLA-linked susceptibility to intractable vasculitis syndrome]. 793 76


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