Lack of association of hla‐drb1 genotype with radiologic progression in japanese patients with early rheumatoid arthritis

Higami, Kenshi; Hakoda, Masayuki; Matsuda, Yuko; Ueda, Hiroyuki; Kashiwazaki, Sadao

doi:10.1002/art.1780401220

Cited by 31 publications

(16 citation statements)

References 21 publications

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“…On the other hand, ValenzuelaCastano et al [20] reported no relationship between SE and the severity of structural joint damage in large joints. In 1997, we demonstrated that SE alleles failed to correlate with more severe disease [7]. In our current study, we used 123 of these 198 patients, showing a contradiction in the results.…”

Section: Discussioncontrasting

confidence: 69%

“…The patients were derived from those reported in our previous study [7]; thus, they visited our outpatient clinic at the Institute of Rheumatology, Tokyo Women's Medical University, within 1 year of symptom onset and were enrolled in a prospective follow-up study between 1991 and 1995. For this study, we used 123 of 198 patients, who satisfied the American College of Rheumatology (ACR) 1987 criteria for RA [8].…”

Section: Methodsmentioning

confidence: 99%

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Combining effects of polymorphism of tumor necrosis factor α 5′-flanking region and HLA-DRB1 on radiological progression in patients with rheumatoid arthritis

et al. 2008

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We examined whether polymorphisms upstream of the TNF-alpha gene (TNFA) were associated with the radiological progression of rheumatoid arthritis (RA). One hundred and twenty-three patients with early RA (disease duration <1 year) were enrolled in a prospective follow-up study. The laboratory findings (ESR, CRP, and RF) were evaluated every 2 months for 2 years. Radiological progression in hands/wrists and feet was evaluated every 6 months for 2 years using Larsen's score. HLA-DRB1 genotype was determined by PCR-RFLP method. The genotypes for -1031, -863, and -857 single-nucleotide polymorphisms in the upstream 5'-flanking region of TNFA were determined by a PCR-preferential homoduplex formation assay in patients with RA and 265 healthy controls. Four TNFA alleles (U01, U02, U03, and U04) were identified. The frequency of individuals with U02 was significantly higher in patients than in controls (P = 0.0025). Radiographs of hands/wrists/feet were available for 72 patients after 1 year and for 73 patients after 2 years. When the HLA-DRB1 genotype was analyzed simultaneously, patients possessing U02 without an HLA-DRB1 shared epitope (SE) (U02+SE-) showed the lowest progression of Larsen's score (12 months). There was no difference in the level of ESR, CRP, or RF at the first visit among U02+SE+, U02+SE-, U02-SE+, and U02-SE- groups. The combination of the polymorphism of the TNFA upstream promoter region and HLA-DRB1 allele was associated with radiological progression in the early stage of RA.

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Section: Discussioncontrasting

confidence: 69%

Section: Methodsmentioning

confidence: 99%

Combining effects of polymorphism of tumor necrosis factor α 5′-flanking region and HLA-DRB1 on radiological progression in patients with rheumatoid arthritis

et al. 2008

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“…Although the shared epitope hypothesis was initially proposed to explain genetic susceptibility to RA, subsequent investigations have suggested that the primary role of the shared epitope may be involved in the development of more severe manifestations. Numerous studies have pursued clarification of this relationship, but so far, no consensus has been reached (Weyand et al 1992;Vehe et al 1994;Benazet et al 1995;Higami et al 1997;Kim et al 1997;Wassmuth and Wagner 2002;Del Rincon et al 2003;Gorman et al 2004;Goronzy et al 2004). These inconclusive results may be related to ethnic and clinical heterogeneity between patient populations.…”

Section: Discussionmentioning

confidence: 92%

The association of HLA-DRB1 alleles with rheumatoid arthritis in the Chinese Shantou population: a follow-up studyThis paper is one of a selection of papers in this Special Issue, entitled International Symposium on Recent Advances in Molecular, Clinical, and Social Medicine, and has undergone the Journal's usual peer-review process.

Lin

Chen

Xiao

et al. 2007

Biochem. Cell Biol.

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We investigated the distribution of HLA-DRB1 alleles in a sample of the Chinese Shantou population, and explored the relationship between HLA-DRB1 alleles and the susceptibility and clinical features of rheumatoid arthritis (RA). We studied 117 consecutive patients with RA and control groups, including 38 cases of systemic lupus erythematosus and 100 healthy individuals. HLA-DRB1 genotyping was performed using PCR with sequence-specific primers. HLA-DRB1*04 subtypes were detected using spot hybridization of PCR products with sequence-specific oligonucleotide probes. We compared the frequency of HLA-DRB1 alleles in healthy control patients with that in patients with RA. Patients with RA were evaluated for sex, age at disease onset, disease duration, extra-articular involvement, presence of autoantibodies, global functional status, and radiographic damage. The frequency of HLA-DRB1*04 was found to be significantly higher in RA patients than in healthy individuals (49.6% vs 18.0%, odds ratio = 4.478, P< 0.001). HLA-DRB1*0405 was the most prominently associated subtype in RA patients (62.1% vs 27.8%, odds ratio = 4.255, P = 0.011). Compared with the HLA-DRB1*04-negative RA group, the mean duration of RA in the HLA-DRB1*04-positive RA group was longer, and the mean age at disease onset was lower. A 2-9 year follow-up study was performed, and the risk factors associated with the radiographic progression of RA were determined. Logistic regression analysis revealed that only HLA-DRB1*04 alleles were significantly associated with the radiographic progression of RA (B = 2.652, P = 0.018, Exp(B) = 14.182). Our observations indicated that the HLA-DRB1*04 alleles, especially the subtype HLA-DRB1*0405, were significantly associated with RA susceptibility in the Chinese Shantou population. The HLA-DRB1*04 alleles may be associated with the severity of RA.

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“…There has also been the suggestion that there is a hierarchy of risk associated with various SE alleles and allele combinations, with DR␤1*0401 carrying the highest risk of destructive disease (9,21). Interestingly, SE was not associated with erosions in a Japanese cohort of early RA patients, although the prevalence of DR␤1*0401 in this population was low (22). We therefore attempted to clarify whether SE alleles, either alone or in combination with other HLA alleles, were a risk factor for the development of early erosions in our cohort.…”

Section: Discussionmentioning

confidence: 99%

Association of HLA alleles and clinical features in patients with synovitis of recent onset

El‐Gabalawy

Goldbach‐Mansky

Smith

et al. 1999

Arthritis & Rheumatism

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Objective. To determine how HLA alleles are associated with the clinical disease patterns of patients with synovitis of recent onset. Methods. The HLA alleles A, B, C, DR1, and DQ1 were determined in a cohort of 211 patients (mean age 42 years, 64% female, 79% white) with recent-onset synovitis in 1 or more peripheral joints. At a mean disease duration of 33 weeks, 98 patients (46%) met the American College of Rheumatology (ACR) criteria for rheumatoid arthritis (RA), 38 (18%) met the European Spondylarthropathy Study Group criteria for spondylarthropathy (SpA), and 75 (36%) were classified as having undifferentiated arthropathy (UA). Controls were racially matched healthy individuals (n 244). Results. Shared epitope (SE) alleles were significantly more common in rheumatoid factor-positive (RF) patients fulfilling the ACR RA criteria than in other patients with early arthritis (65% versus 35%; P < 0.001). In addition, the RA patients had by far the highest frequency of radiographic erosions (52% and 39% in RF and RF RA, respectively, versus 3% and 9% in SpA and UA patients, respectively; P < 0.0001). The presence of SE alleles was a particularly strong predictor of early erosions in the RF RA patients (odds ratio [OR] 6.8, 95% confidence interval [95% CI] 1.2-45). The presence of 2 SE alleles or an associated DQ1*0301 (DQ7) or DQ1*0302 (DQ8) allele appeared to modestly increase the risk of early erosions, although these DQ alleles were in strong linkage disequili-brium with DR1*0401, both in the patient and in the control populations. B27 was linked with the presence of SE alleles in the patients, including those patients fulfilling the RA criteria, but not in the controls (12% versus 3%; P < 0.001). Enthesitis was present in 23 (11%) of 211 patients, was highly associated with B27 (OR 4.2, 95% CI 1.5-11.5), and surprisingly, was not a feature specific only to the SpA group. The B8-DR3 haplotype was significantly increased in the patient subgroups compared with controls (17% versus 7%; P < 0.01), although the clinical significance of this association is unclear. Conclusion. This study of HLA associations in a diverse cohort of early synovitis patients emphasizes the complex degree of genetic interaction between alleles at several major histocompatibility complex loci, which regulates clinical phenotypes. In particular, SE and B27, while predisposing patients to characteristic clinical syndromes, had an unexpected degree of association in this cohort, perhaps explaining the overlap in clinical features in many patients. Synovitis in 1 or more peripheral joints is the presenting feature of several chronic inflammatory ar-thropathies. The clinical spectrum of rheumatoid arthritis (RA) and the seronegative spondylarthropathies (SpA), which are disorders presumably having distinct pathogenetic mechanisms, can be difficult to differentiate early in the disease course. Moreover, a large proportion of patients with synovitis of recent onset lack specific diagnostic features and are classified as having undifferentiated ...

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Lack of association of hla‐drb1 genotype with radiologic progression in japanese patients with early rheumatoid arthritis

Cited by 31 publications

References 21 publications

Combining effects of polymorphism of tumor necrosis factor α 5′-flanking region and HLA-DRB1 on radiological progression in patients with rheumatoid arthritis

Combining effects of polymorphism of tumor necrosis factor α 5′-flanking region and HLA-DRB1 on radiological progression in patients with rheumatoid arthritis

Association of HLA alleles and clinical features in patients with synovitis of recent onset

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