{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T11:41:49Z","timestamp":1788522109273,"version":"build-2803163510"},"reference-count":34,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"R&D Activity Programs and Synergistic R&D Projects in the Community of Madrid"},{"DOI":"10.13039\/501100004587","name":"Carlos III Health Institute","doi-asserted-by":"crossref","award":["Y2020\/BIO-6600"],"award-info":[{"award-number":["Y2020\/BIO-6600"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Systemic lupus erythematosus (SLE) is a complex autoimmune disease with a multifactorial origin involving genetic, epigenetic, and environmental determinants as well as some risk factors. Genetic predisposition has been quantified through polygenic risk scores (PRS), which integrate the cumulative effect of multiple single nucleotide variants (SNVs) associated with disease risk. Despite extensive research on immune and inflammatory pathways in SLE, the interplay between genetic susceptibility and metabolic dysfunction remains poorly understood. This study aimed to explore associations between SLE-related PRS and metabolic, inflammatory, and clinical parameters in adults participating in the METAINFLAMACI\u00d3N-CM project (Hospital Universitario Puerta de Hierro Majadahonda, Madrid, Spain). Methods: Ninety-three participants were included: 56 SLE patients and 37 individuals with metabolic syndrome (MetS) as a reference group. PRS were computed based on validated lupus-associated SNVs. Results: SLE patients showed a distinct metabolic profile compared with the MetS group, characterized by lower BMI, visceral fat, blood pressure, glucose, and liver enzyme levels. Within the SLE cohort, PRS values varied markedly and correlated with specific clinical and biochemical features. Linear regression models revealed a significant inverse association between PRS in SLE and ferritin levels, whereas other metabolic and inflammatory markers (glucose, IL-6, LDL, CRP, neutrophils) were directly influenced by clinical factors. Conclusions: Polygenic predisposition contributes to variability in SLE metabolic phenotype but does not independently drive most inflammatory parameters. SLE patients displayed metabolic and inflammatory alterations relevant to cardiovascular risk, highlighting the importance of comprehensive cardiometabolic assessment. Integrating PRS with metabolic profiling may support precision personalized management and improve cardiovascular risk evaluation in SLE.<\/jats:p>","DOI":"10.3390\/genes17010053","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T12:23:44Z","timestamp":1767356624000},"page":"53","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Polygenic Risk and Linked Metabolic Profile in Systemic Lupus Erythematosus: Cross-Sectional Insights"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8680-6704","authenticated-orcid":false,"given":"Andrea","family":"Higuera-G\u00f3mez","sequence":"first","affiliation":[{"name":"Department of Pharmacy and Nutrition, Faculty of Biomedical and Health Sciences, Universidad Europea de Madrid, Calle Tajo s\/n, Villaviciosa de Od\u00f3n, 28670 Madrid, Spain"},{"name":"Precision Nutrition and Cardiometabolic Health, IMDEA-Food Institute (Madrid Institute for Advanced Studies), Campus of International Excellence (CEI) UAM+CSIC, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda","family":"Mart\u00ednez-Urbistondo","sequence":"additional","affiliation":[{"name":"Internal Medicine Service, Puerta de Hierro University Hospital of Majadahonda, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amanda","family":"Cuevas-Sierra","sequence":"additional","affiliation":[{"name":"Precision Nutrition and Cardiometabolic Health, IMDEA-Food Institute (Madrid Institute for Advanced Studies), Campus of International Excellence (CEI) UAM+CSIC, 28049 Madrid, Spain"},{"name":"Red Iberoamericana de Colaboraci\u00f3n Acad\u00e9mica y Cient\u00edfica en Nutri\u00f3micas y Nutrici\u00f3n de Precisi\u00f3n (RINN22), 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"de Cuevillas","sequence":"additional","affiliation":[{"name":"Precision Nutrition and Cardiometabolic Health, IMDEA-Food Institute (Madrid Institute for Advanced Studies), Campus of International Excellence (CEI) UAM+CSIC, 28049 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4579-2294","authenticated-orcid":false,"given":"Ulises","family":"De la Cruz-Mosso","sequence":"additional","affiliation":[{"name":"Red Iberoamericana de Colaboraci\u00f3n Acad\u00e9mica y Cient\u00edfica en Nutri\u00f3micas y Nutrici\u00f3n de Precisi\u00f3n (RINN22), 28049 Madrid, Spain"},{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Laboratorio de Evaluaci\u00f3n del Estado Nutricio, Centro de Investigaci\u00f3n en Educaci\u00f3n y Bienestar Universitario, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina F.","family":"Nicoletti","sequence":"additional","affiliation":[{"name":"Red Iberoamericana de Colaboraci\u00f3n Acad\u00e9mica y Cient\u00edfica en Nutri\u00f3micas y Nutrici\u00f3n de Precisi\u00f3n (RINN22), 28049 Madrid, Spain"},{"name":"Center of Lifestyle Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9095-4868","authenticated-orcid":false,"given":"Jhulia C. N. L.","family":"da Mota","sequence":"additional","affiliation":[{"name":"Center of Lifestyle Medicine, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo 01246-903, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Mellor-Pita","sequence":"additional","affiliation":[{"name":"Internal Medicine Service, Puerta de Hierro University Hospital of Majadahonda, 28222 Majadahonda, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Alonso-Bern\u00e1ldez","sequence":"additional","affiliation":[{"name":"ADNTRO Genetics, Carretera Betlem, s\/n, Colonia de Sant Pere, 07579 Arta, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0680-0802","authenticated-orcid":false,"given":"Barbara","family":"Vizmanos","sequence":"additional","affiliation":[{"name":"Red Iberoamericana de Colaboraci\u00f3n Acad\u00e9mica y Cient\u00edfica en Nutri\u00f3micas y Nutrici\u00f3n de Precisi\u00f3n (RINN22), 28049 Madrid, Spain"},{"name":"Red de Inmunonutrici\u00f3n y Gen\u00f3mica Nutricional en las Enfermedades Autoinmunes, Departamento de Neurociencias, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"},{"name":"Laboratorio de Evaluaci\u00f3n del Estado Nutricio, Centro de Investigaci\u00f3n en Educaci\u00f3n y Bienestar Universitario, Centro Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara 44340, Jalisco, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5218-6941","authenticated-orcid":false,"given":"J. Alfredo","family":"Mart\u00ednez","sequence":"additional","affiliation":[{"name":"Precision Nutrition and Cardiometabolic Health, IMDEA-Food Institute (Madrid Institute for Advanced Studies), Campus of International Excellence (CEI) UAM+CSIC, 28049 Madrid, Spain"},{"name":"Red Iberoamericana de Colaboraci\u00f3n Acad\u00e9mica y Cient\u00edfica en Nutri\u00f3micas y Nutrici\u00f3n de Precisi\u00f3n (RINN22), 28049 Madrid, Spain"},{"name":"Biomedical Research Centre for Obesity Physiopathology and Nutrition Network (CIBEROBN), Instituto de Salud Carlos III (ISCIII), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1056\/NEJMra1100359","article-title":"Systemic lupus erythematosus","volume":"365","author":"Tsokos","year":"2011","journal-title":"N. Engl. J. 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