{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T15:33:12Z","timestamp":1782228792698,"version":"3.54.5"},"reference-count":42,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T00:00:00Z","timestamp":1690416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"China Medical University Hospital in Taiwan","award":["DMR-110-023"],"award-info":[{"award-number":["DMR-110-023"]}]},{"name":"China Medical University Hospital in Taiwan","award":["DMR-112-126"],"award-info":[{"award-number":["DMR-112-126"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Rheumatoid arthritis (RA) is a systemic disease characterized by non-infectious inflammation of the joints and surrounding tissues, which can cause severe health problems, affect the patient\u2019s daily life, and even cause death. RA can be clinically diagnosed by the occurrence of blood serological markers, rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibody (anti-CCP). However, about 20% of RA patients exhibit negative results for both markers, which makes RA diagnosis difficult and, therefore, may delay the effective treatment. Previous studies found some evidence that human leukocyte antigen (HLA)-related genes might be the susceptibility genes for RA and their polymorphisms might contribute to varieties of susceptibility and disease severity. This study aimed for the genetic polymorphisms of the RA patient genome and their effects on the RA patient\u2019s serological makers, RF and anti-CCP. A total of 4580 patients\u2019 electronic medical records from 1992 to 2020 were retrieved from the China Medical University Hospital database. The most representative single-nucleotide polymorphisms (SNPs) were identified through a genome-wide association study (GWAS) followed by enzyme-linked immunosorbent assay (ELISA) validation using the blood from 30 additional RA patients. The results showed significant changes at the position of chromosome 6 with rs9270481 being the most significant locus, which indicated the location of the HLA-DRB1 gene. Further, patients with the CC genotype at this locus were more likely to exhibit negative results for RF and anti-CCP than those with the TT genotype. The C allele was also more likely to be associated with negative results for RF and anti-CCP. The results demonstrated that a genetic polymorphism at rs9270481 affected the expression of RF and anti-CCP in RA patients, which might indicate the necessity to develop a personalized treatment plan for each individual patient based on the genetic profile.<\/jats:p>","DOI":"10.3390\/ijms241512036","type":"journal-article","created":{"date-parts":[[2023,7,28]],"date-time":"2023-07-28T01:51:47Z","timestamp":1690509107000},"page":"12036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Effects of Human Leukocyte Antigen DRB1 Genetic Polymorphism on Anti-Cyclic Citrullinated Peptide (ANTI-CCP) and Rheumatoid Factor (RF) Expression in Rheumatoid Arthritis (RA) Patients"],"prefix":"10.3390","volume":"24","author":[{"given":"Yu-Chia","family":"Chen","sequence":"first","affiliation":[{"name":"Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung-Ming","family":"Huang","sequence":"additional","affiliation":[{"name":"Division of Immunology and Rheumatology, Department of Internal Medicine, China Medical University Hospital, Taichung 404, Taiwan"},{"name":"School of Chinese Medicine, China Medical University, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2729-0541","authenticated-orcid":false,"given":"Ting-Yuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Million-Person Precision Medicine Initiative, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences, Southeastern Oklahoma State University, Durant, OK 74701, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Jung","family":"Chan","sequence":"additional","affiliation":[{"name":"Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng-Yu","family":"Shih","sequence":"additional","affiliation":[{"name":"Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hsin-Han","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Plastic and Reconstructive Surgery, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6925-7627","authenticated-orcid":false,"given":"Shih-Yin","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1373-245X","authenticated-orcid":false,"given":"Fuu-Jen","family":"Tsai","sequence":"additional","affiliation":[{"name":"School of Chinese Medicine, China Medical University, Taichung 404, Taiwan"},{"name":"Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung 404, Taiwan"},{"name":"Department of Medical Genetics, China Medical University Hospital, Taichung 404, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1316","DOI":"10.1136\/annrheumdis-2013-204627","article-title":"The global burden of rheumatoid arthritis: Estimates from the global burden of disease 2010 study","volume":"73","author":"Cross","year":"2014","journal-title":"Ann. 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