{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T07:37:14Z","timestamp":1767339434883,"version":"3.41.2"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Aim<\/jats:title><jats:p><jats:italic>NPHS2<\/jats:italic>is the coding gene of podocin. This study aims to investigate the association between<jats:italic>NPHS2<\/jats:italic>p.R229Q (rs61747728), the most frequently reported missense variant of<jats:italic>NPHS2<\/jats:italic>, and focal segmental glomerular sclerosis (FSGS) or steroid-resistant nephrotic syndrome (SRNS) based on typing the variant in a Chinese FSGS\/SRNS cohort and conducting a meta-analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We recruited patients with FSGS or SRNS and healthy individuals. To conduct a meta-analysis, all studies on p.R229Q and FSGS\/SRNS were searched from public databases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In total, we enrolled 204 patients with FSGS, 61 patients with SRNS [46 with FSGS, 9 with minimal change disease (MCD), and six patients with IgA nephropathy (IgAN)], and 100 healthy controls. Unexpectedly, p.R229Q was absent in the patients from our cohort. By meta-analysis of 21 studies including 2,489 patients with FSGS\/SRNS and 6,004 healthy controls, we confirmed that the A allele of p.R229Q was significantly associated with increased risk of FSGS\/SRNS (allelic OR = 1.9, 95% CI = 1.44-2.52,<jats:italic>P<\/jats:italic>&amp;lt; 0.001). However, the subgroup analysis showed that the association between p.R229Q and FSGS\/SRNS was true only in Caucasians (allelic OR = 2.14, 95%CI = 1.54-2.98,<jats:italic>P<\/jats:italic>&amp;lt; 0.001) and in early-onset patients (allelic OR: 2.13, 95% CI = 1.21-3.76,<jats:italic>P<\/jats:italic>= 0.009).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>NPHS2<\/jats:italic>p.R229Q may play an important role in enhancing the susceptibility of FSGS\/SRNS, especially in ethnicity of Caucasian and age of early-onset patients.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2022.937122","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T14:12:42Z","timestamp":1658499162000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Association Between NPHS2 p.R229Q and Focal Segmental Glomerular Sclerosis\/Steroid-Resistant Nephrotic Syndrome"],"prefix":"10.3389","volume":"9","author":[{"given":"Qiongxiu","family":"Zhou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qinjie","family":"Weng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunzi","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Tong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xu","family":"Hao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hao","family":"Shi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pingyan","family":"Shen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hong","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyuan","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.1007\/s00467-009-1138-5","article-title":"Long-term 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