MHC2TA is associated with rheumatoid arthritis in Japanese patients.
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ABSTRACT:
SUBMITTER: Iikuni N
PROVIDER: S-EPMC1798499 | biostudies-literature | 2007 Feb
REPOSITORIES: biostudies-literature
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MHC2TA is associated with rheumatoid arthritis in Japanese patients.
Iikuni Noriko N Ikari Katsunori K Momohara Shigeki S Tomatsu Taisuke T Hara Masako M Yamanaka Hisashi H Okamoto Hiroshi H Kamatani Naoyuki N
Annals of the rheumatic diseases 20061107 2
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Project description:For the optimum efficacy of disease-modifying anti-rheumatic drugs (DMARDs), patients need to be adherent to their medication regimen. To clarify the effects of medication adherence on disease activity in Japanese patients with rheumatoid arthritis (RA), we conducted a cohort study in patients with various stages of RA. Patients were enrolled from the Kyoto University RA Management Alliance cohort, and followed up prospectively for 12 months. In this study, a total of 475 patients were analyzed and divided into 9 groups according to their medication adherence and the RA disease duration. The primary outcomes were based on the rate of a disease flare. The secondary outcomes were the changes in disease activity score using 28 joints (DAS28-ESR), simplified disease activity index (SDAI) and physical disability by health assessment questionnaire-disability index (HAQ). The changes in DAS28-ESR, HAQ, and the risk of disease flare in the highly adherent patients were significantly lower than those of the less adherent patients among the groups with RA ? 4.6 years but not those among the other groups. Taken together, this study identified a significant association between medication adherence and the disease flare during early-stage RA or short disease duration. These results emphasize the need to pay more attention to medication adherence in preventing the disease progression of RA.
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Project description:Rheumatoid arthritis (RA) is a common, chronic autoimmune disease affecting 0.5-1.0% of adults worldwide, including approximately 4.5-5.0 million patients in China. The genetic etiology and pathogenesis of RA have not yet been fully elucidated. Recently, one new RA susceptibility gene (RAD51B) has been identified in Korean and European populations. In this study, we designed a two-stage case-control study to further assess the relationship of common variants in the RAD51B gene with increased risk of RA in a total of 965 RA patients and 2,511 unrelated healthy controls of Han Chinese ancestry. We successfully identified a common variant, rs911263, as being significantly associated with the disease status of RA (P = 4.8 × 10-5, OR = 0.64). In addition, this SNP was shown to be related to erosion, a clinical assessment of disease severity in RA (P = 2.89 × 10-5, OR = 0.52). These findings shed light on the role of RAD51B in the onset and severity of RA. More research in the future is needed to clarify the underlying functional link between rs911263 and the disease.
| S-EPMC5374468 | biostudies-literature
Project description:BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic inflammatory status, joint destruction, disability, and pain. Methotrexate (MTX) has been confirmed to reduce disease activity and delay or stabilize the development of bone erosions. However, major drawbacks are that patients show great interindividual variability in response to MTX and the unpredictable occurrence of side effects. A strategy for personalized MTX treatment to predict its efficacy and toxicity has not yet been determined. To establish personalized MTX therapy in Japanese patients with rheumatoid arthritis, we performed a preliminary study for predicting better methotrexate efficacy including single-nucleotide polymorphisms (SNPs) for MTX-related transporters/enzymes.MethodsDisease control status (good or poor) was judged by the number of Disease Activity Scores (DAS28) of <2 for 6-12 months. The response index R was calculated by the improved area under the curve (AUC) of the DAS28 score for 0-3 or 0-6 months by dividing the cumulative dose of MTX during 0-3 or 0-6 months, respectively. Genotyping of alleles of RFC1 80G > A, RFC1 -43 T > C, FPGS 1994G > A, GGH 401C > T, MTHFR 1298A > C, and TYMS 3'-UTR (-6/+6) was performed using the real-time PCR system.ResultsSeven of 21 patients were judged as good responders in terms of disease control, and the remainder as poor responders. For 0-3 months after starting MTX administration, the median cumulative dose and improved DAS28 AUC in the good and poor response groups were 96.0 mg and 25.4 and 118.0 mg and 23.4, respectively. For 0-6 months, the median cumulative dose and improved DAS28 AUC in the good and poor response groups were 192.0 mg and 51.0 and 214.0 mg and 47.6, respectively. Statistically significant differences between the 2 groups in the 0-6-month period were observed in DAS28 AUC improvement and index R. A slight tendency for a correlation between G/G genotypes and A allele genotypes in RFC1 80 genotypes was observed, although it did not reach statistical significance.ConclusionThis study suggested that aggressive RA treatment with MTX from the early period of administration is necessary to obtain a good response after 6 months, although no SNPs predicting a better treatment response to MTX were identified.
| S-EPMC4895805 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a chronic systemic inflammatory disease. Certain HLA-DRB1 "shared-epitope" alleles are reported to be positively associated with increased RA susceptibility, whereas some of the other alleles may be negatively associated. However, studies on the latter are rare. Here, we focus on the protective effects of DRB1 alleles in Japanese RA patients in an association study. Relative predispositional effects (RPE) were analyzed by sequential elimination of carriers of each allele with the strongest association. The protective effects of DRB1 alleles were investigated in patients stratified according to whether they possessed anti-citrullinated peptide antibodies (ACPA). The DRB1*13:02 allele was found to be negatively associated with RA (P = 4.59×10(-10), corrected P (Pc) = 1.42×10(-8), odds ratio [OR] 0.42, 95% CI 0.32-0.55, P [RPE] = 1.27×10(-6)); the genotypes DRB1*04:05/*13:02 and *09:01/*13:02 were also negatively associated with RA. The protective effect of *13:02 was also present in ACPA-positive patients (P = 3.95×10(-8), Pc = 1.22×10(-6), OR 0.42, 95%CI 0.31-0.58) whereas *15:02 was negatively associated only with ACPA-negative RA (P = 8.87×10(-5), Pc = 0.0026, OR 0.26, 95%CI 0.12-0.56). Thus, this study identified a negative association of DRB1*13:02 with Japanese RA; our findings support the protective role of DRB1*13:02 in the pathogenesis of ACPA-positive RA.
| S-EPMC4049831 | biostudies-literature
Project description:An association between major histocompatibility complex (MHC) genes, particularly those within the class II HLA region, and rheumatoid arthritis (RA) is well established, and accounts for an estimated 30% of the genetic component in RA. The MHC class II transactivator gene (MHC2TA) on chromosome 16p13 has recently emerged as the most important transcription factor regulating genes required for class II MHC-restricted antigen presentation. Previous studies of a promoter region polymorphism (-168A/G, rs3087456) in the MHC2TA gene and RA have yielded conflicting results.To assess the association of the MHC2TA -168A/G polymorphism (rs3087456) and risk for RA by meta-analysis.Meta-analysis was performed for 6861 patients with RA and 9270 controls from 10 case-control studies. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each study. Summary ORs and 95% CIs were calculated for random effects models.No effect was observed for the G risk allele (OR 1.02, 95% CI 0.93 to 1.12, p = 0.70) or the GG risk genotype (OR 1.14, 95% CI 0.95 to 1.36, p = 0.16).Our results indicate that the MHC2TA -168A/G polymorphism (rs3087456) is not associated with RA yet underscore the importance of including shared epitope allele carrier status, secondary phenotypes and more complete characterisation of MHC2TA variation in future studies.
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Project description:BackgroundRheumatoid arthritis (RA) is characterized by systemic synovitis with bone erosion and joint cartilage degradation. Although the analysis of polymorphisms in cytokine-encoding genes is important or understanding the pathophysiology of RA and selecting appropriate treatment for it, few studies have examined such single-nucleotide polymorphisms (SNPs) specifically in Japanese patients. This study was established to investigate the associations between polymorphisms in cytokine-encoding genes, autoantibodies and therapeutic responses in Japanese RA patients.MethodsThe subjects in this study consisted of 100 RA patients and 50 healthy controls. We extracted data on sex, age, disease duration, rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody, and therapeutic responses, including to methotrexate (MTX) and biological disease-modifying antirheumatic drugs (DMARDs). Genomic DNA was isolated from peripheral blood, which was genotyped for IL-10, TNF-α, TGF-β1, and IFN-γ polymorphisms.ResultsRegarding IL-10 (-592 C/A and -819 C/T), significant decreases in the frequencies of the IL-10 (-592) CC genotype and (-819) CC genotype were found in RA patients compared with the levels in controls. For IFN-γ (+874 T/A), a significant decrease in the frequency of the TT genotype was found in RA patients compared with that in controls. Regarding TGF-β1 (+869 T/C), patients with positivity for anti-CCP antibody had a significantly lower frequency of the CC genotype than those with negativity for it. Furthermore, the IL-10 (-592) CC genotype and (-819) CC genotype might be related to the biological DMARD-response.ConclusionOur results suggest that the analysis of polymorphisms in cytokine-encoding genes may be useful when selecting treatment for Japanese RA patients.
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Project description:ObjectiveTo perform a postmarketing surveillance study evaluating the safety and effectiveness of abatacept in Japanese patients with rheumatoid arthritis (RA).MethodsSafety and effectiveness data were collected for all RA patients (at 772 sites) treated with intravenous abatacept between September 2010 and June 2011. Patients were treated by the approved dosing regimen according to the package insert. Treatment effectiveness was evaluated at baseline and at weeks 4, 12, and 24 using Disease Activity Score 28 (DAS28) according to erythrocyte sedimentation rate or serum C-reactive protein concentrations.ResultsOverall, 3882 and 3016 abatacept-naïve RA patients were included in safety and effectiveness analyses, respectively. Adverse drug reactions (ADRs) were reported for 15.66% of patients and serious ADRs were detected for 2.52% of patients. The incidence of serious infections was 1.03% and these were mainly attributed to different types of bacterial pneumonia. Disease activity improved significantly over 6 months. Separate multivariate analysis identified predictors of severe ADR, and severe infections and factors predictive of clinically meaningful DAS28 improvement after 6 months of treatment with abatacept.ConclusionsAbatacept was efficacious and well tolerated in a clinical setting. No new safety concerns were detected.
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Project description:ObjectivesThe prevalence of chronic kidney disease (CKD) was reported to be higher in rheumatoid arthritis (RA) patients than in normal healthy individuals. Human leukocyte antigen (HLA) was associated with RA or CKD. Few studies on the association of HLA with CKD in RA have been reported. Here, we investigated the association of HLA polymorphisms with CKD in Japanese RA patients.MethodsHLA-DRB1 genotyping was conducted in 351 Japanese RA patients with CKD (estimated glomerular filtration rate [eGFR] lower than 60 [mL/min/1.73 m2]) and 959 without CKD (eGFR equal to or higher than 60 [mL/min/1.73 m2]). Associations of allele carrier frequencies of DRB1 with CKD were examined in the RA patients.ResultsThere was an association of DRB1*13:02 with CKD in RA, but this did not achieve statistical significance (p = 0.0265, odds ratio [OR] 1.70, pc = 0.7412, 95% confidence interval [CI] 1.09-2.64). The DR6 serological group was associated with CKD in RA (p = 0.0008, OR 1.65, 95% CI 1.24-2.20). A gene-dosage effect of DR6 was not detected. Logistic regression analysis showed that the association of DR6 with CKD in RA was independent of clinical characteristics.ConclusionsThe present study first revealed the independent predisposing association of DR6 with CKD in Japanese RA patients, although DR6 is known to be protective against RA. Our data suggest direct or indirect roles of HLA for the development of CKD in RA, but the mechanisms are not clear.
| S-EPMC10379419 | biostudies-literature
Project description:Rheumatoid arthritis (RA) is a complex, multifactorial disorder with an autoimmune etiology. RA is highly heritable and is associated with both human leucocyte antigen (HLA) and non-HLA genes. We investigated the associations of 33 single nucleotide polymorphisms (SNPs) with RA in the Saudi population.MethodsThis study included 105 patients with RA and an equal number of age- and sex-matched controls. The patients with RA attended outpatient clinics at King Khalid University Hospital in Riyadh, Saudi Arabia. Blood samples were collected, and DNA was extracted using Qiagen kits. Primers were designed for the 33 selected SNPs using the MassEXTEND primers program, and samples were genotyped on the Sequenom MassARRAY iPLEX platform. The allele frequencies and genotypes were determined for each SNP, and the results obtained for the patients were compared to those for the controls.ResultsThe allele and genotype frequencies of six SNPs were significantly associated with RA: rs1188934, rs10919563, rs3087243, rs1980422, rs10499194, and rs629326. The minor alleles of rs1188934, rs10919563, rs10499194, and rs629326 were protective, with odds ratios of 0.542, 0.597, 0.589, and 0.625, and p-values of 0.002, 0.023, 0.013 and 0.036, respectively. In addition, the heterozygote frequencies of two SNPs (rs6859219 and rs11586238) were significantly higher in the controls than in the patients.ConclusionsThere is considerable heterogeneity in the genetics of RA in different populations, and the SNPs that are associated with RA in some populations are not in others. We studied 33 SNPs and only eight were associated with RA. The remaining SNPs showed no allelic or genotypic associations with RA.
| S-EPMC10419658 | biostudies-literature
Project description:Rheumatoid arthritis (RA, MIM 180300) is a chronic and complex autoimmune disease. Using the North American Rheumatoid Arthritis Consortium (NARAC) data set provided in Genetic Analysis Workshop 16 (GAW16), we used the genotype-trait distortion (GTD) scores and proposed analysis procedures to capture the gene-gene interaction effects of multiple susceptibility gene regions on RA. In this paper, we focused on 27 RA candidate gene regions (531 SNPs) based on a literature search. Statistical significance was evaluated using 1000 permutations. HLADRB1 was found to have strong marginal association with RA. We identified 14 significant interactions (p < 0.01), which were aggregated into an association network among 12 selected candidate genes PADI4, FCGR3, TNFRSF1B, ITGAV, BTLA, SLC22A4, IL3, VEGF, TNF, NFKBIL1, TRAF1-C5, and MIF. Based on our and other contributors' findings during the GAW16 conference, we further studied 24 candidate regions with 336 SNPs. We found 23 significant interactions (p-value < 0.01), nine interactions in addition to our initial findings, and the association network was extended to include candidate genes HLA-A, HLA-B, HLA-C, CTLA4, and IL6. As we will discuss in this paper, the reported possible interactions between genes may suggest potential biological activities of RA.
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