{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,25]],"date-time":"2025-12-25T07:21:01Z","timestamp":1766647261718,"version":"build-2065373602"},"reference-count":26,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T00:00:00Z","timestamp":1689724800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japan Society for the Promotion of Science","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"the Ministry of Health, Labour, and Welfare of Japan","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Japan Agency for Medical Research and Development","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"National Hospital Organization","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Daiwa Securities Health Foundation","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Japan Research Foundation for Clinical Pharmacology","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"The Nakatomi Foundation","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Takeda Science Foundation","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Mitsui Sumitomo Insurance Welfare Foundation","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Bristol-Myers Squibb Co.","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Abbott Japan Co., Ltd.","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Bristol-Myers K.K.","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Astellas Pharma Inc.","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Chugai Pharmaceutical Co., Ltd.","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Eisai Co., Ltd.","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Mitsuibishi Tanabe Pharma Corporation","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Merck Sharp and Dohme Inc.","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Pfizer Japan Inc.","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Takeda Pharmaceutical Company Limited","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]},{"name":"Teijin Pharma Limited","award":["26293123","22591090","15K09543","18K08402","24791018"],"award-info":[{"award-number":["26293123","22591090","15K09543","18K08402","24791018"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Objectives: The 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. Methods: HLA-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. Results: There 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\u20132.64). The DR6 serological group was associated with CKD in RA (p = 0.0008, OR 1.65, 95% CI 1.24\u20132.20). 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. Conclusions: The 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.<\/jats:p>","DOI":"10.3390\/genes14071470","type":"journal-article","created":{"date-parts":[[2023,7,19]],"date-time":"2023-07-19T21:20:14Z","timestamp":1689801614000},"page":"1470","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Associations of HLA Polymorphisms with Chronic Kidney Disease in Japanese Rheumatoid Arthritis Patients"],"prefix":"10.3390","volume":"14","author":[{"given":"Takashi","family":"Higuchi","sequence":"first","affiliation":[{"name":"Department of Rheumatology, National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose 204-8585, Japan"},{"name":"Department of Nephrology, Ushiku Aiwa General Hospital, 896 Shishiko-cho, Ushiku 300-1296, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shomi","family":"Oka","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose 204-8585, Japan"},{"name":"Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1353-8056","authenticated-orcid":false,"given":"Hiroshi","family":"Furukawa","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose 204-8585, Japan"},{"name":"Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kota","family":"Shimada","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan"},{"name":"Department of Rheumatic Diseases, Tokyo Metropolitan Tama Medical Center, 2-8-29 Musashi-dai, Fuchu 183-8524, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Atsushi","family":"Hashimoto","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan"},{"name":"Department of Internal Medicine, Sagami Seikyou Hospital, 6-2-11 Sagamiohno, Minami-ku, Sagamihara 252-0303, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akiko","family":"Komiya","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan"},{"name":"Department of Clinical Laboratory, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshihiro","family":"Matsui","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan"},{"name":"Department of Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naoshi","family":"Fukui","sequence":"additional","affiliation":[{"name":"Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan"},{"name":"Department of Life Sciences, Graduate School of Arts and Sciences, The University of Tokyo, 3-8-1 Komaba, Meguro-ku, Tokyo 153-8902, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shigeto","family":"Tohma","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, National Hospital Organization Tokyo National Hospital, 3-1-1 Takeoka, Kiyose 204-8585, Japan"},{"name":"Clinical Research Center for Allergy and Rheumatology, National Hospital Organization Sagamihara National Hospital, 18-1 Sakuradai, Minami-ku, Sagamihara 252-0392, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/art.1780330113","article-title":"Subclinical renal dysfunction in rheumatoid arthritis","volume":"33","author":"Boers","year":"1990","journal-title":"Arthritis Rheum."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1136\/ard.60.4.327","article-title":"A prospective study of renal disease in patients with early rheumatoid arthritis","volume":"60","author":"Koseki","year":"2001","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2089","DOI":"10.1007\/s10067-007-0625-y","article-title":"Prognosis of clinical renal disease and incidence of new renal findings in patients with rheumatoid arthritis: Follow-up of a population-based study","volume":"26","author":"Karstila","year":"2007","journal-title":"Clin. Rheumatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"350","DOI":"10.1093\/rheumatology\/kem370","article-title":"Kidney disease in RA patients: Prevalence and implication on RA-related drugs management: The MATRIX study","volume":"47","author":"Karie","year":"2008","journal-title":"Rheumatology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1258\/rsmsmj.54.2.9","article-title":"The prevalence of chronic kidney disease in rheumatology outpatients","volume":"54","author":"Hill","year":"2009","journal-title":"Scott. Med. J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1053\/j.ajkd.2013.08.010","article-title":"Development of reduced kidney function in rheumatoid arthritis","volume":"63","author":"Hickson","year":"2014","journal-title":"Am. J. Kidney Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"331","DOI":"10.3109\/14397595.2015.1088620","article-title":"Prevalence of chronic kidney disease and administration of RA-related drugs in patients with RA: The NinJa 2012 study in Japan","volume":"26","author":"Saisho","year":"2016","journal-title":"Mod. Rheumatol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1002\/art.1780380213","article-title":"Renal biopsy findings and clinicopathologic correlations in rheumatoid arthritis","volume":"38","author":"Helin","year":"1995","journal-title":"Arthritis Rheum."},{"key":"ref_9","first-page":"154","article-title":"Analysis of renal pathology and drug history in 158 Japanese patients with rheumatoid arthritis","volume":"50","author":"Nakano","year":"1998","journal-title":"Clin. Nephrol."},{"doi-asserted-by":"crossref","unstructured":"Kochi, M., Kohagura, K., Shiohira, Y., Iseki, K., and Ohya, Y. (2016). Inflammation as a Risk of Developing Chronic Kidney Disease in Rheumatoid Arthritis. PLoS ONE, 11.","key":"ref_10","DOI":"10.1371\/journal.pone.0160225"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.kint.2017.11.025","article-title":"Treatment of rheumatoid arthritis with biologic agents lowers the risk of incident chronic kidney disease","volume":"93","author":"Sumida","year":"2018","journal-title":"Kidney Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1097\/00002281-199805000-00007","article-title":"The genetic contribution to the pathogenesis of rheumatoid arthritis","volume":"10","author":"Reveille","year":"1998","journal-title":"Curr. Opin. Rheumatol."},{"doi-asserted-by":"crossref","unstructured":"Oka, S., Furukawa, H., Kawasaki, A., Shimada, K., Sugii, S., Hashimoto, A., Komiya, A., Fukui, N., Ito, S., and Nakamura, T. (2014). Protective effect of the HLA-DRB1*13:02 allele in Japanese rheumatoid arthritis patients. PLoS ONE, 9.","key":"ref_13","DOI":"10.1371\/journal.pone.0099453"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1038\/jhg.2015.36","article-title":"Human leukocyte antigen polymorphisms and personalized medicine for rheumatoid arthritis","volume":"60","author":"Furukawa","year":"2015","journal-title":"J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e31856","DOI":"10.1097\/MD.0000000000031856","article-title":"HLA types and their association with end-stage renal disease in Vietnamese patients: A cross-sectional study","volume":"101","author":"Ong","year":"2022","journal-title":"Medicine"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1111\/iji.12566","article-title":"Systematic review of associations between HLA and renal function","volume":"49","author":"Lowe","year":"2022","journal-title":"Int. J. Immunogenet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/art.1780310302","article-title":"The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis","volume":"31","author":"Arnett","year":"1988","journal-title":"Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1002\/art.27584","article-title":"2010 Rheumatoid arthritis classification criteria: An American College of Rheumatology\/European League Against Rheumatism collaborative initiative","volume":"62","author":"Aletaha","year":"2010","journal-title":"Arthritis Rheum."},{"key":"ref_19","first-page":"71","article-title":"Establishment of B-cell lines derived from 996 Japanese individuals","volume":"23","author":"Kamatani","year":"2004","journal-title":"Tissue Cult. Res. Commun."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1038\/jhg.2015.23","article-title":"Japan PGx Data Science Consortium Database: SNPs and HLA genotype data from 2994 Japanese healthy individuals for pharmacogenomics studies","volume":"60","author":"Kamitsuji","year":"2015","journal-title":"J. Hum. Genet."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1053\/j.ajkd.2008.12.034","article-title":"Revised equations for estimated GFR from serum creatinine in Japan","volume":"53","author":"Matsuo","year":"2009","journal-title":"Am. J. Kidney Dis."},{"doi-asserted-by":"crossref","unstructured":"Oka, S., Furukawa, H., Yasunami, M., Kawasaki, A., Nakamura, H., Nakamura, M., Komori, A., Abiru, S., Nagaoka, S., and Hashimoto, S. (2017). HLA-DRB1 and DQB1 alleles in Japanese type 1 autoimmune hepatitis: The predisposing role of the DR4\/DR8 heterozygous genotype. PLoS ONE, 12.","key":"ref_22","DOI":"10.1371\/journal.pone.0187325"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1471-8286.2007.01931.x","article-title":"genepop\u2019007: A complete re-implementation of the genepop software for Windows and Linux","volume":"8","author":"Rousset","year":"2008","journal-title":"Mol. Ecol. Resour."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1001\/jama.1949.02900430001001","article-title":"Therapeutic criteria in rheumatoid arthritis","volume":"140","author":"Steinbrocker","year":"1949","journal-title":"J. Am. Med. Assoc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"9916","DOI":"10.1038\/s41598-022-14116-x","article-title":"Predisposition of HLA-DRB1*04:01\/*15 heterozygous genotypes to Japanese mixed connective tissue disease","volume":"12","author":"Oka","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"23","DOI":"10.4137\/BMI.S13654","article-title":"HLA-DRB1*08:02 is associated with bucillamine-induced proteinuria in Japanese rheumatoid arthritis patients","volume":"9","author":"Furukawa","year":"2014","journal-title":"Biomark. Insights"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/7\/1470\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:14:47Z","timestamp":1760127287000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/14\/7\/1470"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,7,19]]},"references-count":26,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7]]}},"alternative-id":["genes14071470"],"URL":"https:\/\/doi.org\/10.3390\/genes14071470","relation":{},"ISSN":["2073-4425"],"issn-type":[{"type":"electronic","value":"2073-4425"}],"subject":[],"published":{"date-parts":[[2023,7,19]]}}}