{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T17:03:11Z","timestamp":1790960591693,"version":"4.1.0"},"reference-count":40,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T00:00:00Z","timestamp":1623369600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003711","name":"Ministry of Science and Technology","doi-asserted-by":"publisher","award":["MOST 107-2314-B-039-053-MY3"],"award-info":[{"award-number":["MOST 107-2314-B-039-053-MY3"]}],"id":[{"id":"10.13039\/501100003711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Adult-onset Still\u2019s disease (AOSD) is a rare autoinflammatory disease, which has elevated autophagosome levels regulated by autophagy-related gene (ATG) expression. We investigated the associations of ATG polymorphisms with AOSD susceptibility, clinical manifestations, and disease course. The six-candidate single-nucleotide polymorphisms (SNPs) involved in autophagy were genotyped using direct sequencing on samples from 129 AOSD patients and 129 healthy participants. The differentially expressed gene products were quantified using PCR and ELISA. Significant linkage disequilibrium was noted in three SNPs of autophagy-related 16-like 1 (ATG16L1) gene (rs10210302, rs2241880, and rs1045100). Although the AA\/CC\/TT haplotype of ATG16L1 was not associated with the susceptibility of our AOSD patients compared with other haplotypes, those carrying this haplotype had lower mRNA expression levels of LC3-II, reflecting by autophagosome formation (p = 0.026). Patients carrying AA\/CC\/TT haplotype also have a significantly higher proportion of skin rash and a lower proportion of arthritis compared with other haplotypes. The AA\/CC\/TT haplotype was significantly associated with systemic pattern (odds ratio, 3.25; 95% confidence interval, 1.15\u20139.14; p = 0.026). In summary, the AA\/CC\/TT haplotype encoded lower levels of autophagosome formation and was associated with a higher proportion of skin rash and systemic pattern of AOSD compared with other haplotypes.<\/jats:p>","DOI":"10.3390\/genes12060904","type":"journal-article","created":{"date-parts":[[2021,6,11]],"date-time":"2021-06-11T12:44:37Z","timestamp":1623415477000},"page":"904","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["The Association of ATG16L1 Variations with Clinical Phenotypes of Adult-Onset Still\u2019s Disease"],"prefix":"10.3390","volume":"12","author":[{"given":"Wei-Ting","family":"Hung","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Department of Medical Education, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6531-5538","authenticated-orcid":false,"given":"Shuen-Iu","family":"Hung","sequence":"additional","affiliation":[{"name":"Cancer Vaccine and Immune Cell Therapy Core Laboratory, Chang Gung Immunology Consortium, Chang Gung Memorial Hospital, Linkou, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7593-3065","authenticated-orcid":false,"given":"Yi-Ming","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research, Taichung Veterans General Hospital, Taichung 40705, Taiwan"},{"name":"School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chia-Wei","family":"Hsieh","sequence":"additional","affiliation":[{"name":"Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan"},{"name":"Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7304-4587","authenticated-orcid":false,"given":"Hsin-Hua","family":"Chen","sequence":"additional","affiliation":[{"name":"Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan"},{"name":"Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan"},{"name":"Department of Industrial Engineering and Enterprise Information, Tunghai University, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5468-1329","authenticated-orcid":false,"given":"Kuo-Tung","family":"Tang","sequence":"additional","affiliation":[{"name":"School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Rong Hsing Research Center for Translational Medicine & Ph.D. Program in Translational Medicine, National Chung Hsing University, Taichung 40227, Taiwan"},{"name":"Division of Allergy, Immunology, and Rheumatology, Taichung Veterans General Hospital, Taichung 40705, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Der-Yuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Translational Medicine Laboratory, Rheumatology and Immunology Center, China Medical University Hospital, Taichung 40447, Taiwan"},{"name":"Rheumatology and Immunology Center, China Medical University Hospital, Taichung 40447, Taiwan"},{"name":"School of Medicine, China Medical University, Taichung 40447, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2796-1026","authenticated-orcid":false,"given":"Tsuo-Hung","family":"Lan","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei 11221, Taiwan"},{"name":"Tsao-Tun Psychiatric Center, Ministry of Health and Welfare, Nantou 54249, Taiwan"},{"name":"Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli 35053, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1136\/ard.30.2.121","article-title":"Still\u2019s disease of the adults","volume":"30","author":"Bywaters","year":"1971","journal-title":"Ann. 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