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In this study, we investigated the relationship between HLA system and children with SSNSWR and SDNS\/FRNS and clarified the value of HLA allele detection for precise typing of childhood SSNS.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>A total of 241 Chinese Han individuals with SSNS were genotyped using GenCap-WES Capture Kit, and four-digit resolution HLA alleles were imputed from available Genome Wide Association data. The distribution and carrying frequency of HLA alleles in SSNSWR and SDNS\/FRNS were investigated. Additionally, logistic regression and mediating effects were used to examine the relationship between risk factors for disease process and HLA system.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Compared with SSNSWR, significantly decreased serum levels of complement 3 (C3) and complement 4 (C4) at onset were detected in SDNS\/FRNS (C3, <jats:italic>P<\/jats:italic>\u2009&lt;\u20090.001; C4, <jats:italic>P<\/jats:italic>\u2009=\u20090.018). The average time to remission after sufficient initial steroid treatment in SDNS\/FRNS was significantly longer than that in SSNSWR (<jats:italic>P<\/jats:italic>\u2009=\u20090.0001). Low level of C4 was further identified as an independent risk factor for SDNS\/FRNS (<jats:italic>P<\/jats:italic>\u2009=\u20090.008, odds ratio\u2009=\u20090.174, 95% confidence interval 0.048\u20130.630). The <jats:italic>HLA-A*11:01<\/jats:italic> allele was independently associated with SSNSWR and SDNS\/FRNS (<jats:italic>P<\/jats:italic>\u2009=\u20090.0012 and <jats:italic>P<\/jats:italic>\u2009=\u20090.0006, respectively). No significant HLA alleles were detected between SSNSWR and SDNS\/FRNS. In addition, a mediating effect among HLA-I alleles (<jats:italic>HLA-B*15:11<\/jats:italic>, <jats:italic>HLA-B*44:03<\/jats:italic> and <jats:italic>HLA-C*07:06<\/jats:italic>), C4 level and SDNS\/FRNS was identified.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>HLA-I alleles provide novel genetic markers for SSNSWR and SDNS\/FRNS. HLA-I antigens may be involved in steroid dependent or frequent relapse in children with SSNS as mediators of immunoregulation.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s12519-021-00489-y","type":"journal-article","created":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T07:16:29Z","timestamp":1641021389000},"page":"109-119","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Association between HLA alleles and sub-phenotype of childhood steroid-sensitive nephrotic syndrome"],"prefix":"10.1007","volume":"18","author":[{"given":"Hao","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fen-Fen","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Ying","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi-Pin","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huan","family":"Chi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye-Tao","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue-Lan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bao-Hui","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Li","family":"Wan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Jiao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dao-Qi","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gao-Fu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mo","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Ping","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Chan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-7168","authenticated-orcid":false,"given":"Qiu","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,1,1]]},"reference":[{"key":"489_CR1","first-page":"724","volume":"42","author":"JY Yang","year":"2004","unstructured":"Yang JY, Yao Y, Chinese Society of Pediatric Nephrology. 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