ArticlePloS one2013
PADI4 and HLA-DRB1 are genetic risks for radiographic progression in RA patients, independent of ACPA status: results from the IORRA cohort study.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Associations between C677T and A1298C polymorphisms of MTHFR and susceptibility to rheumatoid arthritis: a systematic review and meta-analysis.Rheumatology international · 2017Pooled it
- Polygenic risk scores of rheumatoid arthritis associated with seropositivity and bone erosions in a Taiwanese population.Scientific reports · 2025Article
- Autocitrullination confers monocyte chemotactic properties to peptidylarginine deiminase 4.Scientific reports · 2023Article
- Heavy Chain Constant Region Usage in Antibodies to Peptidylarginine Deiminase 4 as a Marker of Disease Subsets in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2022Article
- A genome-wide association study identifying the SNPs predictive of rapid joint destruction in patients with rheumatoid arthritis.Biomedical reports · 2021Article
- Joint Surgery in Tunisian Rheumatoid Arthritis Patients: Prevalence and Risk Factors.Archives of rheumatology · 2020Article
- FEATURE SELECTION FOR GENERALIZED VARYING COEFFICIENT MIXED-EFFECT MODELS WITH APPLICATION TO OBESITY GWAS.The annals of applied statistics · 2020Article
- Cytokines (IL-15, IL-21, and IFN-γ) in rheumatoid arthritis: association with positivity to autoantibodies (RF, anti-CCP, anti-MCV, and anti-PADI4) and clinical activity.Clinical rheumatology · 2019Article
- An Autoimmune Disease-Associated Risk Variant in theJournal of clinical microbiology · 2018Article
- Hypoxia‑induced autophagy is inhibited by PADI4 knockdown, which promotes apoptosis of fibroblast‑like synoviocytes in rheumatoid arthritis.Molecular medicine reports · 2018Article
- Joint damage is amplified in rheumatoid arthritis patients with positive thyroid autoantibodies.PeerJ · 2018Article
- NLRP1, PTPN22 and PADI4 gene polymorphisms and rheumatoid arthritis in ACPA-positive Singaporean Chinese.Rheumatology international · 2017Article
- Time-averaged disease activity fits better joint destruction in rheumatoid arthritis.Scientific reports · 2017Article
- Genetics of rheumatoid arthritis susceptibility, severity, and treatment response.Seminars in immunopathology · 2017Review
- Increased autophagy in fibroblast-like synoviocytes leads to immune enhancement potential in rheumatoid arthritis.Oncotarget · 2017Article
- Recent Advances in Defining the Genetic Basis of Rheumatoid Arthritis.Annual review of genomics and human genetics · 2016Review
- Decreased severity of experimental autoimmune arthritis in peptidylarginine deiminase type 4 knockout mice.BMC musculoskeletal disorders · 2016Article
- Rheumatoid Factor Is Associated With the Distribution of Hand Joint Destruction in Rheumatoid Arthritis.Arthritis & rheumatology (Hoboken, N.J.) · 2015Article
- Peptidylarginine deiminase type 4 deficiency reduced arthritis severity in a glucose-6-phosphate isomerase-induced arthritis model.Scientific reports · 2015Article
- Genetic studies of rheumatoid arthritis.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2015Review
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
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Abstract
introductionRheumatoid arthritis (RA) is a systemic, chronic inflammatory disease influenced by both genetic and environmental factors, leading to joint destruction and functional impairment. Recently, a large-scaled GWAS meta-analysis using more than 37,000 Japanese samples were conducted and 13 RA susceptibility loci were identified. However, it is not clear whether these loci have significant impact on joint destruction or not. This is the first study focused on the 13 loci to investigate independent genetic risk factors for radiographic progression in the first five years from onset of RA.
methodsSharp/van der Heijde score of hands at 5-year disease duration, which represents joint damage, were measured retrospectively and used as an outcome variable in 865 Japanese RA patients. Genetic factors regarded as putative risk factors were RA-susceptible polymorphisms identified by the Japanese GWAS meta-analysis, including HLA-DRB1 (shared epitope, SE), rs2240340 (PADI4), rs2230926 (TNFAIP3), rs3093024 (CCR6), rs11900673 (B3GNT2), rs2867461 (ANXA3), rs657075 (CSF2), rs12529514 (CD83), rs2233434 (NFKBIE), rs10821944 (ARID5B), rs3781913 (PDE2A-ARAP1), rs2841277 (PLD4) and rs2847297 (PTPN2). These putative genetic risk factors were assessed by a stepwise multiple regression analysis adjusted for possible non-genetic risk factors: autoantibody positivity (anti-citrullinated peptide antibody [ACPA] and rheumatoid factor), history of smoking, gender and age at disease onset.
resultsThe number of SE alleles (P = 0.002) and risk alleles of peptidyl arginine deiminase type IV gene (PADI4, P = 0.04) had significant impact on progressive joint destruction, as well as following non-genetic factors: ACPA positive (P = 0.0006), female sex (P = 0.006) and younger age of onset (P = 0.02).
conclusionsIn the present study, we found that PADI4 risk allele and HLA-DRB1 shared epitope are independent genetic risks for radiographic progression in Japanese rheumatoid arthritis patients. The results of this study give important knowledge of the risks on progressive joint damage in RA patients.
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