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)

Rheumatoid arthritis (RA) is associated with HLA-DR4 and DR1 antigens. HLA-DRB1 gene sequences analysis demonstrated that only a limited set of alleles is positively associated with RA. Third hypervariable region sequences (70-74, 86) Q(R)R(K)RAA, G(V) are found in up to 95% of erosive RA. The presence of disease-associated allels may predict severe outcome of the disease. Therefore, their presence may allow us to start aggressive therapy in early stage of the disease.
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PMID:[The role of MHC class II genes in the etiopathogenesis of rheumatoid arthritis]. 1022 66

A nine years prospective study was performed on 82 Spanish rheumatoid arthritis patients with a disease duration of less than two years at the study entry, in order to evaluate the role of HLA markers in the susceptibility and progression of rheumatoid arthritis. Radiological evaluation of disease severity was performed at the time of diagnosis and 9 years later. High resolution HLA-DR typing demonstrated that the presence of the shared epitope (SE) was more frequent among patients (61% vs. 31% in controls; p = 0.00003; OR = 3.48). Fourteen patients carried two SE+ HLA-DRB1 alleles (SE+/+); 36, one single allele (SE+/-) and 32 were SE negative (SE-/-). HLA-DR4 (particularly DRB1*0401 and DRB 1*0405) and HLA-DR10 were increased among patients. At study entry, the frequencies of locally severe (hands and feet) RA were more frequent among SE+/+ patients (79%) than among SE+/- (47%) and SE-/-(44%) patients (p = 0.05; RR = 1.80). After 9 years of disease these differences disappeared, whereas differences in the extent of the disease arise: 79%, 50% and 32% of SE+/+, SE+/- and SE-/- patients respectively showed large joints involvement (shoulders, elbows, hips and knees) (p = 0.01; RR = 2.44 for SE+/+ vs. SE-/-; and p = 0.04; RR = 1.81 for SE+ vs. SE-). These results suggest that the presence of the shared epitope is associated with the extent and progression of radiological joint damage in rheumatoid arthritis.
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PMID:Association of HLA shared epitope with joint damage progression in rheumatoid arthritis. 1032 62

Rheumatoid arthritis (RA) is a common disease of unknown aetiology which usually causes progressive destruction of the joints. Familial aggregation, twin studies and segregation analyses suggest that there is a genetic component to RA and the HLA-DRB1 locus in the major histocompatibility complex on chromosome 6 has been shown to be linked to, and associated with, RA susceptibility. It is likely that other genes with weaker effects are also involved, which may be difficult to detect using conventional parametric and non-parametric linkage methods. We have implemented the combined sib-TDT and TDT, in addition to parametric and non-parametric linkage methods, to investigate the candidate genes of the interleukin-1 (IL-1) gene cluster on chromosome region 2q13, since IL-1 is an important cytokine in the control of the inflammatory response that is central to RA pathology. Several tightly linked IL-1 cluster markers yielded suggestive evidence for linkage in the combined TDT in those families in which affected siblings did not share two HLA-DRB1 alleles identical by descent. The evidence was significant in those with severe disease, as assessed by the presence of bone erosions. In contrast, there was no evidence of linkage using non-parametric linkage analysis, but parametric analysis revealed weak evidence of linkage when marker-trait disequilibrium was incorporated into the analysis. The data provide preliminary evidence for linkage of genes of the IL-1 cluster to RA and suggest a possible role for this region in severe erosive disease.
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PMID:Combined sib-TDT and TDT provide evidence for linkage of the interleukin-1 gene cluster to erosive rheumatoid arthritis. 1044 34

Polymorphisms in the 5'-flanking promoter/enhancer region of the tumor necrosis factor (TNF)-a gene were examined to study the genetic background of rheumatoid arthritis (RA). Four variant alleles, -1,031C/ -863A, -1,031C/-238A, -857T and -308A, were identified and examined in 387 RA patients and 575 healthy Japanese controls. The frequency of the -857T allele in RA patients was significantly higher than that in the controls. However, the HLA-DRB1 analysis in the same subjects showed that the DRB1*0405 allele, which is in linkage disequilibrium with the -857T, was more strongly associated with the disease susceptibility than the -857T allele. These results suggest that the susceptible gene to RA is more closely linked to the HLA-DRB1 locus than to the TNF-alpha locus.
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PMID:Polymorphisms in the 5'-flanking region of tumor necrosis factor-alpha gene in patients with rheumatoid arthritis. 1048 48

The HLA-DMA gene, along with the HLA-DMB gene, encodes the not classical class II molecule. This molecule catalyzes the class-II-associated invariant-chain peptide (CLIP)-antigen peptide exchange in classical class II molecule peptide-binding groove. As such, the DM heterodimer is an antigen presentation regulator and may be linked to immune system deficiencies such as those observed in autoimmune diseases. The study of DMA gene polymorphism seems be a reasonable approach to provide an answer to this question. Thanks to PCR-derived methods, the relationship between DMA gene polymorphism and rheumatoid arthritis (RA) was demonstrated in the present study. The DMA*0101 allele was observed to confer a significant predisposition to RA while the DMA*0102 allele significantly protected from this disease. Polymorphism experiments with the HLA-DRB1 gene revealed that this relationship between DMA polymorphism and RA is not a consequence of a linkage disequilibrium with the HLA-DRB1 alleles implicated in this pathology. The study of the DMA gene could therefore prove to be very useful in the early diagnosis of RA.
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PMID:HLA-DMA alleles are possible new markers of rheumatoid arthritis: study of a Corsican group. 1057 73

We followed 138 Spanish patients (37 men and 101 women) with rheumatoid arthritis (RA) to analyze whether patient sex influenced the HLA-DRB1 associations with disease susceptibility. Results showed that, although a high increase of the shared epitope (SE) was observed in both genders, distribution of HLA-DRB1 specificities differs from males to females: DR1 was increased among male patients, whereas DR4 as well as DR10 were preferentially associated with female RA. To further explore whether this phenomenon operates either on susceptibility or on disease progression, 82 patients (25 males and 57 females) among the whole group were followed during the first 8 to 10 years of their disease. Results from this prospective study showed that the association of the SE with radiological disease severity was found in both male and female patients, although it was stronger among the latter group. Interestingly, DR1- as well as DR4-related alleles contributed to the high frequency of SE among female patients with early small-joints severe RA and/or long-term large-joint erosions. These results suggest that HLA polymorphism might be involved in RA pathogenesis through two mechanisms: (a) in combination with patient sex, operating in disease induction; and (b) independent of patient sex, influencing disease severity and progression.
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PMID:Complex associations between HLA-DRB1 genes and female rheumatoid arthritis: results from a prospective study. 1062 40

We have investigated HLA region microsatellite polymorphisms in rheumatoid arthritis (RA) which are known to be associated with HLA class II alleles in the Korean population. Ninety patients with RA and 106 controls were employed for this study, in which TAP1CA, DQCAR, D6S273, HLA-DRB1, -DQA1 and -DQB1 allele typing were performed. DQCAR 113 (RR = 3.2, P<0.0002), DQCAR 115 (RR = 3.6, P<0.0001) and heterozygous DQCAR 113/115 (RR = 11.2, P<0.0001) frequencies were significantly increased in the RA group compared with the control group. The HLA-DRB1 genotypes of patients who had DQCAR 113/115 alleles were defined as DRB1*04 and/or DRB1*09. There was no significant difference between RA and controls in D6S273 and TAP1CA allele frequencies. We demonstrated that HLA-DRB1*0405 (RR = 6.6, P<10(-6)), DQA1*03 (RR = 5.2, P<10(-6)), DQB1*04 (RR = 3.5, P<0.002) alleles were useful markers of susceptibility to RA in Koreans. The frequency of HLA-DRB1*0405 was higher in DQCAR 113 allele-positive RA (68.1%) than in DQCAR 113 allele-negative (16.3%) and total RA (43.3%) groups, and the susceptibility risk of DQCAR 113 allele to RA was more increased in the DRB1*0405-positive group (RR = 5.5, P<0.04). On the other hand, DQCAR 115 allele was more significantly associated with susceptibility to RA in HLA-DRB1*0405-negative patients (RR = 5.1, P<0.0005), and the association between RA and HLA-DRB1*0405 was also significantly associated with DQCAR 115 allele-negative patients (RR = 13.2, P<0.00001) as compared with DQCAR 115 allele-negative control groups. HLA-DRB1*0405-DQA1*03-DQCAR113-DQB1*03 haplotype showed high relative risk value (RR= 17.7, P<0.0002). In conclusion, the DQCAR allele in combination with HLA class II, especially DR, is probably a useful risk marker for RA susceptibility in the Korean population.
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PMID:DQCAR 113 and DQCAR 115 in combination with HLA-DRB1 alleles are significant markers of susceptibility to rheumatoid arthritis in the Korean population. 1067 68

CTLA-4 is considered to be one of the attractive candidates for the susceptibility genes to rheumatic diseases. In the present study, the association of CTLA-4 polymorphism with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) was examined in the Japanese population using the case-control association analysis. Polymerase chain reaction-preferential homoduplex formation assay (PCR-PHFA) was applied for the screening of genetic variations and for the genotyping of a large number of samples. A greater proportion of Japanese patients with RA (44%) and SLE (44%) compared with healthy individuals (37%) had exon 1 49 G/G genotype, but the difference did not reach statistical significance. However, when the patients with RA and healthy individuals were stratified according to HLA-DRB1 alleles, a weakly significant increase of the positivity of CTLA-4 49G allele was observed in HLA-DRB1*0405-positive patients (87%) compared with DRB1*0405-positive healthy individuals (71%) (P = 0.014, odds ratio = 2.77). These results indicate that CTLA-4 exon 1 polymorphism does not contribute greatly to the susceptibility to RA and SLE, at least in Japanese, although the presence of CTLA4 49G allele could be a minor predisposing factor for RA in HLA-DRB1*0405-positive individuals. In addition, PCR-PHFA was shown to be useful for a mass screening of gene variations.
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PMID:Lack of a strong association of CTLA-4 exon 1 polymorphism with the susceptibility to rheumatoid arthritis and systemic lupus erythematosus in Japanese: an association study using a novel variation screening method. 1067 72

The aim of this study was to investigate whether polymorphisms in the tumor necrosis factor (TNF) and HLA-DRB1 gene regions are independently associated with rheumatoid arthritis (RA) in a population from Lugo region of northwestern Spain. RA patients (n=179) attending hospital outpatient clinics in Lugo, northwestern Spain and matched controls (n=145) were recruited. RA susceptibility in this population was predominantly associated with DRB1*0401, while erosive disease was associated with HLA-DRB1*0101 and DRB1*04. The increase in DRB1*04 was accounted for by an increase in DRB1*0404 and *0405 but not *0401 frequencies. In contrast, *0401 frequency was significantly increased in seropositive patients. The rheumatoid arthritis shared epitope (SE) was associated with increased risk for seropositive and erosive disease and this appeared to operate in a dose-dependent manner. Logistic regression analyses revealed that the TNF microsatellite markers TNFc1 and b3 were associated with RA independently of DRB1*04 and the SE. Carriage of a TNF c1 allele provided an increased risk of RA in SE-negative and SE-heterozygous individuals. TNFc1 and TNFb3 were not associated with erosive or seropositive disease. In contrast, TNF a2 was significantly associated with erosive disease which was independent of DRB1*04 and the SE. Further studies will be needed to establish why (TNFc1) polymorphism seemingly associated with low TNFalpha production, is a risk factor for RA.
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PMID:Different gene loci within the HLA-DR and TNF regions are independently associated with susceptibility and severity in Spanish rheumatoid arthritis patients. 1085 83

Genes in the human leukocyte antigen (HLA) region remain the most powerful disease risk genes in rheumatoid arthritis (RA). Several allelic variants of HLA-DRB1 genes have been associated with RA, supporting a role for T-cell receptor-HLA-antigen interactions in the pathologic process. Disease-associated HLA-DRB1 alleles are similar but not identical and certain allelic variants are preferentially enriched in patient populations with defined clinical characteristics. Also, a gene dosing effect of HLA-DRB1 alleles has been suggested by the accumulation of patients with two RA-associated alleles, especially in patient subsets with a severe disease course. Therefore, polymorphisms in HLA genes are being explored as tools to dissect the clinical heterogeneity of the rheumatoid syndrome. Besides HLA polymorphisms, other risk genes will be helpful in defining genotypic profiles correlating with disease phenotypes. One such phenotype is the type of synovial lesion generated by the patient. HLA genes in conjunction with other genetic determinants may predispose patients to a certain pathway of synovial inflammation. Also, patients may or may not develop extraarticular manifestations, which are critical in determining morbidity and mortality. HLA genes, complemented by other RA risk genes, are likely involved in shaping the T-cell repertoire, including the emergence of an unusual T-cell population characterized by the potential of vascular injury, such as seen in extraarticular RA.
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PMID:Association of MHC and rheumatoid arthritis. HLA polymorphisms in phenotypic variants of rheumatoid arthritis. 1109 29


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