{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T06:37:12Z","timestamp":1776926232228,"version":"3.51.2"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The PI3K\u2013AKT\u2013mTOR signaling pathway plays a central role in immune regulation and has been implicated in autoimmune diseases. However, the contribution of genetic variation within key components of this pathway to microscopic polyangiitis (MPA) remains incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a genetic association study in a Chinese cohort including MPA patients and controls. Four single nucleotide polymorphisms (SNPs) within core genes of the PI3K\u2013AKT\u2013mTOR pathway (PIK3CA, AKT1, and MTOR) were analyzed. A cumulative genetic burden score was constructed by summing the number of risk alleles across loci. Participants were stratified into burden categories based on the distribution in controls. Logistic regression, trend analysis, and sensitivity analyses restricted to hospital-based controls were performed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A high genetic burden within the PI3K-AKT-mTOR pathway was associated with increased susceptibility to MPA, with a significant linear trend across burden categories, whereas the intermediate burden group showed no significant association, suggesting a threshold-dependent effect. In sex\u2212stratified analyses, associations appeared more evident among females, although a formal test for interaction did not indicate statistical significance. Analyses suggest a potential sex-related trend that warrants further investigation. Sensitivity analyses restricted to hospital-based controls yielded consistent results. Several common haplotypes spanning PIK3CA, AKT1, and MTOR were less frequent among patients, indicating potential protective effects. Pathway-level genetic burden was also associated with MPO-ANCA positivity. Single-variant analyses revealed generally concordant but modest effects.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Genetic variation across selected core components of the PI3K--AKT--mTOR pathway may contribute to susceptibility to MPA. The observed patterns, including potential sex-related differences, should be interpreted cautiously and require validation in larger and independent cohorts. These findings highlight a potential pathway-level genetic architecture underlying MPA susceptibility.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1807517","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T05:37:58Z","timestamp":1776922678000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic burden across core genes of the PI3K\u2013AKT\u2013mTOR pathway is associated with susceptibility to microscopic polyangiitis: a Chinese cohort study"],"prefix":"10.3389","volume":"17","author":[{"given":"Lizhen","family":"Li","sequence":"first","affiliation":[{"name":"Department of Nephrology, Hunan Clinical Research Center for Chronic Kidney Disease, Hunan Provincial People\u2019s Hospital, The First Affiliated Hospital of Hunan Normal University","place":["Changsha, China"]},{"name":"Hunan Engineering Research Center for Prevention, Treatment and 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Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinlan","family":"Rao","sequence":"additional","affiliation":[{"name":"Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University","place":["Nanning, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"She","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Hunan Clinical Research Center for Chronic Kidney Disease, Hunan Provincial People\u2019s Hospital, The First Affiliated Hospital of Hunan Normal University","place":["Changsha, 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