{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T16:12:17Z","timestamp":1791994337270,"version":"4.4.0"},"reference-count":70,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T00:00:00Z","timestamp":1700006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Otto-von-Guericke University of Magdeburg, School of Medicine, Germany","award":["SFB854 TP01"],"award-info":[{"award-number":["SFB854 TP01"]}]},{"name":"Otto-von-Guericke University of Magdeburg, School of Medicine, Germany","award":["2498"],"award-info":[{"award-number":["2498"]}]},{"name":"Investigation Committee of the University Thessaly, Greece","award":["SFB854 TP01"],"award-info":[{"award-number":["SFB854 TP01"]}]},{"name":"Investigation Committee of the University Thessaly, Greece","award":["2498"],"award-info":[{"award-number":["2498"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The interleukin-1 gene cluster encodes cytokines, which modulate mesangial cell proliferation and matrix expansion, both constituting central factors in the development and progression of immunoglobulin A nephropathy (IgAN). A candidate-gene study was performed to examine the association of polymorphisms of the interleukin-1 gene cluster with the risk of progressive IgAN. To gain deeper insights into the involvement of interleukin genes in IgAN, a meta-analysis of genetic association studies (GAS) that examine the association between interleukin variants and IgAN was conducted. Association study: The case-control study consisted of 121 unrelated Caucasians with sporadic, histologically diagnosed IgAN and of 246 age- and sex-matched healthy controls. Persistent proteinuria (&gt;2 g\/24 h) and\/or impaired kidney function (serum creatinine &gt; 1.5 mg\/dL) defined progressive (n = 67) vs. non-progressive (n = 54) IgAN cases. Genotypes were assessed for two promoter-region single-nucleotide polymorphisms, C-899T (rs1800587) in IL1A and C-511T (rs16944) in IL1B, and for one penta-allelic variable-length tandem repeat polymorphism (VNTR 86 bp intron 2) in IL1RN. The association of these variants with the susceptibility of IgAN and the development of progressive IgAN (healthy status, IgAN, progressive IgAN) was tested using the generalized odds ratio (ORG) metric. Linkage disequilibrium and haplotype analysis were also performed. Meta-analysis: We included in the meta-analysis 15 studies investigating association between 14 interleukin variants harbored in eight different genes and IgAN. The ORG was used to evaluate the association between interleukin variants and IgAN using random effects models. The present case-control study revealed association of IL1B C-511T (rs16944) with the progression of IgAN (p = 0.041; ORG = 2.11 (1.09\u20134.07)). On haplotype analysis, significant results were derived for the haplotypes C-C-1 (p = 0.005; OR = 0.456 (0.261~0.797)) and C-T-2 (p = 0.003; OR = 4.208 (1.545\u201311.50)). Regarding association and meta-analysis results, variants in IL1B (rs1143627 and rs16944), IL1RN (rs928940, rs439154, and rs315951) and IL10 (rs1800871) were associated with IgAN based on either genotype or allele counts. Genetic variants and haplotypes in the IL1B, IL1RN, and IL10 genes might contribute to an increased risk for development and progression of IgAN.<\/jats:p>","DOI":"10.3390\/ijms242216347","type":"journal-article","created":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T10:51:37Z","timestamp":1700045497000},"page":"16347","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Interleukin Variants Are Associated with the Development and Progression of IgA Nephropathy: A Candidate-Gene Association Study and Meta-Analysis"],"prefix":"10.3390","volume":"24","author":[{"given":"Ioanna","family":"Chronopoulou","sequence":"first","affiliation":[{"name":"Departments of Nephrology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7206-2716","authenticated-orcid":false,"given":"Maria","family":"Tziastoudi","sequence":"additional","affiliation":[{"name":"Departments of Nephrology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Pissas","sequence":"additional","affiliation":[{"name":"Departments of Nephrology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Efthimios","family":"Dardiotis","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, Department of Neurology, University of Thessaly, University Hospital of Larissa, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Dardioti","sequence":"additional","affiliation":[{"name":"Laboratory of Neurogenetics, Department of Neurology, University of Thessaly, University Hospital of Larissa, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon","family":"Golfinopoulos","sequence":"additional","affiliation":[{"name":"Departments of Nephrology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Filippidis","sequence":"additional","affiliation":[{"name":"Departments of Nephrology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter R.","family":"Mertens","sequence":"additional","affiliation":[{"name":"University Clinic for Nephrology and Hypertension, Diabetology and Endocrinology, Medical Faculty, Otto-von Guericke University Magdeburg, 39120 Magdeburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelia E.","family":"Tsironi","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology, Faculty of Medicine, School of Health Sciences, University of Thessaly, University Hospital of Larissa, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7564-2724","authenticated-orcid":false,"given":"Vassilios","family":"Liakopoulos","sequence":"additional","affiliation":[{"name":"2nd Department of Nephrology, AHEPA Hospital, School of Medicine, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9302-1633","authenticated-orcid":false,"given":"Theodoros","family":"Eleftheriadis","sequence":"additional","affiliation":[{"name":"Departments of Nephrology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5515-8089","authenticated-orcid":false,"given":"Ioannis","family":"Stefanidis","sequence":"additional","affiliation":[{"name":"Departments of Nephrology, Faculty of Medicine, School of Health Sciences, University of Thessaly, 41334 Larissa, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16001","DOI":"10.1038\/nrdp.2016.1","article-title":"IgA nephropathy","volume":"2","author":"Lai","year":"2016","journal-title":"Nat. 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