{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:54:45Z","timestamp":1787169285656,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Higher Education Malaysia, Fundamental Research Grant Scheme","award":["FRGS\/1\/2023\/SKK01\/UKM\/02\/1"],"award-info":[{"award-number":["FRGS\/1\/2023\/SKK01\/UKM\/02\/1"]}]},{"award":["FRGS\/1\/2023\/SKK01\/UKM\/02\/1"],"award-info":[{"award-number":["FRGS\/1\/2023\/SKK01\/UKM\/02\/1"]}],"id":[{"id":"https:\/\/ror.org\/05mcs2t73","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Systemic lupus erythematosus (SLE) is a polygenic autoimmune disorder where genetic diversity drives significant clinical heterogeneity. This review summarizes the current understanding of the roles of genetic polymorphisms in immunological dysregulation, organ-specific manifestations and therapeutic response heterogeneity in individuals with SLE. The literature was obtained from PubMed, EBSCOhost, Web of Science and Scopus. The narrative review comprised 60 publications published within the last 12 years. The research consistently identifies the major histocompatibility complex (MHC) region as the most significant genetic risk factor for the onset of autoimmunity. Genetic variants in STAT4 and IRF5 exacerbate disease progression by facilitating chronic inflammation. These genetic factors are associated with various clinical outcomes, including renal and neuropsychiatric symptoms. Polymorphisms in HLA class II, TLR7 and FBN2 are notably linked to serious consequences, including lupus nephritis (LN). Progress in targeted therapy signifies a transition to personalized medicine with medications such as anifrolumab, litifilimab, iberdomide and Janus kinase (JAK) or Cyclin-Dependent Kinase (CDK) inhibitors, demonstrating potential for targeting pathways associated with the interferon gene signature and STAT4 polymorphisms. Notwithstanding the problems presented by the heterogeneity of SLE, the identification of risk variations is anticipated to enhance predictive and therapeutic biomarkers, hence facilitating more precise and individualized disease management.<\/jats:p>","DOI":"10.3390\/ijms27093968","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T13:32:22Z","timestamp":1777469542000},"page":"3968","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Genetic Polymorphisms in Systemic Lupus Erythematosus and Their Clinical Implications: A Narrative Review"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-2385-0647","authenticated-orcid":false,"given":"Audrey Matilda","family":"Egan","sequence":"first","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1953-112X","authenticated-orcid":false,"given":"Nor Adzimah","family":"Johdi","sequence":"additional","affiliation":[{"name":"UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5549-4242","authenticated-orcid":false,"given":"Elena Aisha","family":"Azizan","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rozita","family":"Mohd","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakthiswary","family":"Rajalingham","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Syahrul Sazliyana","family":"Shaharir","sequence":"additional","affiliation":[{"name":"Department of Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0768-7605","authenticated-orcid":false,"given":"Mohamed Afiq Hidayat","family":"Zailani","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia (UKM), Cheras 56000, Kuala Lumpur, Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,29]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Sutanto, H., and Yuliasih, Y. 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