{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T20:28:59Z","timestamp":1785356939553,"version":"3.55.0"},"reference-count":57,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chang Gung Memorial Hospital","award":["CMRPG 5K0131"],"award-info":[{"award-number":["CMRPG 5K0131"]}]},{"name":"Chang Gung Memorial Hospital","award":["CMRPG 5H0022"],"award-info":[{"award-number":["CMRPG 5H0022"]}]},{"name":"Chang Gung Memorial Hospital","award":["CMRPG 3J1422"],"award-info":[{"award-number":["CMRPG 3J1422"]}]},{"name":"Chang Gung Memorial Hospital","award":["CMRPG 5I0061"],"award-info":[{"award-number":["CMRPG 5I0061"]}]},{"name":"Chang Gung Memorial Hospital","award":["MOST 109-2314-B-182-068-MY3"],"award-info":[{"award-number":["MOST 109-2314-B-182-068-MY3"]}]},{"name":"Chang Gung Memorial Hospital","award":["MOST 107-2314-B-182-059-MY3"],"award-info":[{"award-number":["MOST 107-2314-B-182-059-MY3"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["CMRPG 5K0131"],"award-info":[{"award-number":["CMRPG 5K0131"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["CMRPG 5H0022"],"award-info":[{"award-number":["CMRPG 5H0022"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["CMRPG 3J1422"],"award-info":[{"award-number":["CMRPG 3J1422"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["CMRPG 5I0061"],"award-info":[{"award-number":["CMRPG 5I0061"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["MOST 109-2314-B-182-068-MY3"],"award-info":[{"award-number":["MOST 109-2314-B-182-068-MY3"]}]},{"name":"Ministry of Science and Technology, Taiwan","award":["MOST 107-2314-B-182-059-MY3"],"award-info":[{"award-number":["MOST 107-2314-B-182-059-MY3"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Epistasis of ERAP1 single nucleotide variations (SNVs) and HLA-B27 has been linked to ankylosing spondylitis susceptibility (AS). The current study examined how prevalent ERAP1 allelic variants (SNV haplotypes) in Taiwan affect ERAP1 functions and AS susceptibility in the presence or absence of HLA-B27. Sanger sequencing was used to discover all ERAP1 coding SNVs and common allelic variants in Taiwanese full-length cDNAs from 45 human patients. For the genetic association investigation, TaqMan genotyping assays were utilized to establish the genotypes of ERAP1 SNVs in 863 AS patients and 1438 healthy controls. Ex vivo biological analysis of peripheral blood mononuclear cells from homozygous donors of two common-risk ERAP1 allelic variants was performed. Two common-risk ERAP1 allelic variants were also cloned and functionally studied. In Taiwanese, eleven frequent ERAP1 SNVs and six major ERAP1 allelic variants were discovered. We discovered that in Taiwanese, the most prevalent ERAP1-001 variant with 56E, 127R, 276I, 349M, 528K, 575D, 725R, and 730Q interacting with HLA-B27 significantly contributed to the development of AS. In HLA-B27 negative group, however, the second most prevalent ERAP1-002 variant with 56E, 127P, 276M, 349M, 528R, 575D, 725R, and 730E was substantially related with an increased risk of AS. Ex vivo and in vitro research demonstrated that ERAP1 allelic variants have a significant impact on ERAP1 functions, suggesting that ERAP1 plays a role in the development of AS. In an HLA-B27-dependent manner, common ERAP1 allelic variants are related with AS susceptibility.<\/jats:p>","DOI":"10.3390\/cells11152427","type":"journal-article","created":{"date-parts":[[2022,8,7]],"date-time":"2022-08-07T21:03:50Z","timestamp":1659906230000},"page":"2427","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Functional ERAP1 Variants Distinctively Associate with Ankylosing Spondylitis Susceptibility under the Influence of HLA-B27 in Taiwanese"],"prefix":"10.3390","volume":"11","author":[{"given":"Chin-Man","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Rehabilitation, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Kun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeong-Jian","family":"Jan Wu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing-Chi","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Wen","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianming","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Veterinary and Biomedical Sciences, Department of Medicine, University of Minnesota, St. Paul, MN 55108, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Yih","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Allergy, Immunology and Rheumatology, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan City 333, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1097\/BOR.0000000000000179","article-title":"Syndesmophyte growth in ankylosing spondylitis","volume":"27","author":"Tan","year":"2015","journal-title":"Curr. 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