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)

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 frequency of HLA-DRB1 alleles was determined in 68 Caucasoid patients with polymyalgia rheumatica (PMR) and 140 controls using polymerase chain reaction (PCR) sequence-specific oligonucleotide typing. In keeping with previous studies, an increased frequency of DRB1*04 was observed in patients [55.9% vs 35.0%, odds ratio (OR) 2.4, 95% confidence interval (CI) 1.3-4.4]. HLA-DRB1*0101 frequency was also increased in patients, although less confidence could be placed on this association (19.1% vs 14.3%, OR 1.4, 95% CI 0.6-3.3). HLA-DRB1*04 subtyping indicated that the frequencies of both DRB1*0401 (38.2% vs 22.1%, OR 2.2, 95% CI 1.0-4.3) and DRB1*0404 (16.2% vs 5.0%, OR 3.7, 95% CI 1.2-11.1) were specifically raised. An increased frequency of the RA shared epitope (QKRAA/QRRAA) was also observed in this group (75.0% vs 44.2%, OR 3.8, 95% CI 1.9-7.6). When the analysis was restricted to only DRB1*04-negative patients and controls, the frequencies of DRB1*0301, *11 and *08 were marginally raised. However, no obvious relationship appeared to exist between PMR susceptibility and DRB1 alleles carrying the DYF conserved epitope in the second hypervariable region. Autoantibodies to thyroid antigens were present in 23% of patients. An increased frequency of DRB1*0301 was observed in patients with thyroid microsomal antibodies compared to those without (54.5% vs 24.6%, OR 3.7, 95% CI 0.8-17.0). This increase was not observed in patients with thyroglobulin autoantibodies. These data indicate that both DRB1*0401 and *0404 are associated with PMR, and that this may extend to include DRB1*0101. The immunogenetic profile of susceptibility markers in this condition appears to be similar to that in rheumatoid arthritis.
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PMID:Polymyalgia rheumatica is associated with both HLA-DRB1*0401 and DRB1*0404. 867 May 95

The objective was to explore the role of HLA-DRB1 genes in determining disease severity in rheumatoid arthritis (RA). The population comprised extended pedigrees of 17 multicase RA families. Family members were genotyped for both HLA-DRB1 alleles using restriction fragment length polymorphism (RFLP). Identification of HLA-DRB1*04 variants was performed using the Multiplex ARMS-RFLP technique. Compound heterozygote individuals carrying two different alleles containing the shared epitope (SE) were at greatest risk of developing RA (odds ratio = 36, 95% CI 9.1-143). A synergistic or additive effect of these alleles is suggested. Individuals carrying no SE alleles expressed milder disease, as measured by the Spread Severity (SS) index, compared to compound heterozygotes (P = 0.045). Compound heterozygosity was not invariably associated with severe disease with six (50%) having clinically mild disease at a median age of 57.5 yr and median disease duration of 16 yr. Inheriting two different SE-bearing alleles results in an increased risk of RA and, on average, greater disease severity. This is not, however, invariably associated with severe disease, making it of limited use as a predictor of prognosis.
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PMID:Compound heterozygosity for the shared epitope and the risk and severity of rheumatoid arthritis in extended pedigrees. 913 63

The sequence polymorphism of HLA-DRB1 molecules in 84 rheumatoid arthritis (RA) patients with early RA has been analysed to evaluate whether particular HLA-DR alleles influence disease progression in the early stage of the disease. Clinical data were analysed by grouping the patients according to disease-associated haplotype combinations (DRB1*04,04/DRB1*04,01/DRB1*04,X/DRB1*01,X) in comparison to patients who did not carry these haplotypes (DRB1*X,X). Our results indicate that patients with early RA who are homozygous for DRB1*04 exhibit an elevated inflammatory activity and an increase of joint affections. In addition, the amino acid polymorphism (QR/KRAA) at position 70-74 seems to affect the production of rheumatoid factors. These results support the role of HLA-DRB1 alleles in the pathogenesis of RA and indicate that patients with particular HLA-DRB1*04 haplotype combinations may require intensified therapeutic interventions in the early stage of the disease to prevent disease progression.
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PMID:HLA-DRB1*04 subtypes are associated with increased inflammatory activity in early rheumatoid arthritis. 937 88

Rheumatoid arthritis (RA) is associated with the presence of particular HLA-DRB1 alleles. In order to characterize HLA-DQB1 and/or-DPB1 alleles that contribute to disease susceptibility besides HLA-DRB1 alleles, we have analysed the HLA-DRB1, -DQB1 and -DPB1 polymorphism in 84 RA patients and 135 controls. HLA typing for HLA-DRB1 and -DQB1 alleles was performed using sequence-specific primers in combination with sequence-based typing. HLA-DPB1 alleles were characterized by reverse dot-blot hybridization. Our data confirm the predominant role of the (Q)R/KRAA sequence from AA position 70-74 of the HLA-DRB chain for disease susceptibility. In particular, the lysine (K) substitution at position 71 was highly significantly associated with RA. Analysis of the DQB1 locus revealed no association with RA when linkage disequilibrium between HLA-DRB1 and -DQB1 alleles was considered. In contrast, we observed an increased frequency of HLA-DPB1*0401 among (Q)R/KRAA-positive patients. (Q)R/KRAA-negative RA patients exhibited an overrepresentation of HLA-DPB1*0201 and HLA-DPB1*0601. Rheumatoid factor (RF) production correlated with the presence of the disease-associated (Q)R/KRAA amino acid cassette of the HLA-DRB chain. When HLA-DPB1 allele frequencies were compared between RF-positive and RF-negative RA patients, we observed an increased frequency of HLA-DPB1*0401 among RF-positive RA patients and HLA-DPB1*0201 among RF-negative patients. These results suggest that besides the predominent role of HLA-DR molecules in RA, HLA-DP molecules may have an influence on disease susceptibility and could modulate disease progression. HLA-DPB1*0401 may function in addition to HLA-DRB1*04, whereas HLA-DPB1*0201 and -DPB1*0601 may represent additional risk factors among (Q)R/KRAA-negative RA patients.
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PMID:HLA-DR/DQ/DP interactions in rheumatoid arthritis. 944 4

The genetic susceptibility to rheumatoid arthritis is conferred by genes in the human leukocyte antigen (HLA) region on chromosome 6, but additional genes may be involved to determine disease susceptibility. We have studied the distribution of the CTLA4 exon 1 polymorphism (49 A/G) in rheumatoid arthritis. This dimorphism at codon 17 results in an amino acid exchange (Thr/Ala) in the leader peptide of the expressed protein and was analyzed by PCR, SSCP and RFLP in 258 Caucasian rheumatoid arthritis patients and 456 controls. Rheumatoid arthritis patients were characterized by a decreased frequency of homozygotes for the Thr-17 substitution (32% versus 39%) and an overrepresentation of patients heterozygous for the Thr/Ala substitution (54% versus 46%). Gene frequencies for the Ala/Thr substitution differed only marginally from controls. In contrast, analyses of the CTLA4 exon 1 polymorphism with respect to HLA-DRB1*04 revealed significantly more patients with Ala in the homozygous (19% versus 15% controls) or heterozygous state (54% versus 39% controls) and less homozygous for Thr (27% versus 46% controls), with a particular increase of Ala/Ala genotypes among rheumatoid arthritis patients carrying the HLA-DRB1*0401 subtype. Among HLA-DRB1*04 negative rheumatoid arthritis patients, we observed no difference between the allele frequencies of the Ala-17 or Thr-17 substitution.
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PMID:CTLA4 codon 17 dimorphism in patients with rheumatoid arthritis. 945 4

The aim of the study was to evaluate the relationship between the presence of the 'rheumatoid epitope', defined by a sequence motif in the HLA-DRB1 alleles, rheumatoid factor and disease severity in Northern Italian patients with rheumatoid arthritis (RA). Twenty-nine DR4-positive and 57 DR4-negative RA patients were studied. Each DR4-positive patient was matched with two DR4-negative controls of similar disease duration and sex. HLA-DRB1 alleles were determined in the 86 patients and 351 controls from the same geographical area. The patients were retrospectively evaluated for extra-articular features (EAF) and radiographic damage. The rheumatoid epitope was expressed in 45% of patients. No significant differences in the presence of rheumatoid factor, EAF and articular damage were observed between patients with no, one or two doses of epitope. However, the patients encoding the epitope by an HLA-DR4 allele had a higher number of eroded joints and a higher Larsen score compared to those without the epitope. No differences were present between patients expressing HLA-DRB1*01 alleles and those lacking the rheumatoid epitope. Even in the absence of expression of the rheumatoid epitope, seropositive patients had more EAF and more erosive disease compared to those who were seronegative. Even if most Northern Italian RA patients do not express the rheumatoid epitope, the radiological severity of disease is associated with HLA-DRB1*04 alleles.
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PMID:HLA-DRB1 alleles associated with rheumatoid arthritis in Northern Italy: correlation with disease severity. 956 71

We performed serological phenotyping of HLA antigens in 175 patients with rheumatoid arthritis (RA) with (n = 41) and without (n = 134) renal involvement (RI), and DNA typing of HLA class II alleles in 75 patients. Among the patients with RA, the frequency of serologically determined HLA-DR4 was found to be significantly increased (odds ratio: 1.8, confidence interval: 1.3-2.5, p = 2.4x10(-4)). In the patients without RI, the frequency of serological DR4 significantly increased (odds ratio: 2.2, confidence interval: 1.6-3.3, p = 2. 6x10(-5)). On the other hand, among the patients with RI, a serological determinant, DR15, did significantly increase (odds ratio: 2.7, confidence interval: 0.9-8.4, p = 1.2x10(-3)) in comparison to the controls. At the DNA level, we found that the association of Japanese RA patients with serological HLA-DR4 was based on that with a genotype of HLA-DRB1*0405 (odds ratio: 2.4, confidence interval: 1.5-4.0, p = 4.4x10(-4)) and also found an association of HLA-DRB1*1501 (odds ratio: 2.8, confidence interval: 1.2-6.6, p = 0.017) with RA patients having RI. Our results confirmed the association of HLA-DRB1*04 with RA over the ethnic barrier at the DNA level. Our results also suggested a distinct genetic effect of HLA-DRB1*1501 in the aspect of the susceptibility of RI in RA.
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PMID:Association between HLA-DRB1*15 and Japanese patients with rheumatoid arthritis complicated by renal involvement. 993 52

Human endogenous retrovirus (HERV) long terminal repeat (LTR) elements contain regulatory sequences that can influence the expression of adjacent cellular genes, which may contribute to breakdowns of the immune function leading to autoimmune disease. Rheumatoid arthritis (RA) is associated with particular HLA-DR/DQ haplotypes that modulate the pathogenesis of this autoimmune disease. We have therefore studied a solitary LTR element (DQ-LTR3) of the HERV-K family at the HLA-DQB1 locus for a possible disease association among 228 RA patients and 311 unrelated blood donors. The DQ-LTR3 was significantly more frequent among patients (76% vs 33%, OR = 5.07,p < 0.0001), with the majority of patients being heterozygous for the DQ-LTR3 (61% vs 22%, p < 0.0001). HLA-DRB1*04 positive patients did still differ for the presence of the DQ-LTR3 (88% vs 70%, OR = 3.03, p < 0.001), with an increase of both DQ-LTR3 homozygous and heterozygous patients, when compared to DRB1*04 positive controls (p = 0.0015). HLA-DR/DQ genotype analysis among HLA-DRB1*04 positive individuals revealed significantly more DQ-LTR3 homozygotes among HLA-DRB1*04-DQBI*03 homozygous patients (72% vs 27%, P = 0.015), and the number of DQ-LTR3 homozygous (23% vs 19%) and heterozygous (66% vs 53%) individuals was also increased among HLA-DRB1*04 heterozygous patients (p = 0.034). The presence of the DQ-LTR3 element increased both the relative risk and the positive predictive value for either DRB1*04-DQB1*03 positive/negative individuals when compared to the presence of HLA-DRB1*04-DQB1*03 alone. In conclusion, these data suggest that this DQ-LTR3 enhances susceptibility to RA.
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PMID:An endogenous retroviral long terminal repeat at the HLA-DQB1 gene locus confers susceptibility to rheumatoid arthritis. 995 28

To investigate the association of HLA-DRB1 alleles with polymyalgia rheumatica (PMR) and rheumatoid arthritis (RA), 55 patients with PMR without giant cell arteritis, 203 patients with RA and 230 controls, all from the European population of Marseille, were HLA-DRB1 genotyped by PCR-SSO. HLA-DRB1*01 was significantly increased in both the PMR and RA groups compared to controls (35% versus 17%, P(c) < 0.05, and 41% versus 17%, P(c) < 0.001, respectively). HLA-DRB1*04 was significantly increased in the RA group compared to controls (48% versus 23%, P(c) < 0.001) but not in the PMR group. HLA-DRB1*04 subtype frequencies were significantly different between PMR patients and RA patients. Shared epitope-positive HLA-DRB1*04 alleles (DRB1*0401, 0404, 0405, 0408) were significantly overrepresented in RA patients compared to PMR patients and shared epitope-negative HLA-DRB1*04 alleles were overrepresented in PMR patients compared to RA patients. In conclusion, in the Mediterranean population studied, HLA-DRB1*01 is associated with RA and PMR whereas HLA-DRB1*04 is associated with RA only.
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PMID:DRB1 alleles in polymyalgia rheumatica and rheumatoid arthritis in southern France. 1125 89


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