{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T19:45:13Z","timestamp":1783712713083,"version":"3.55.0"},"reference-count":25,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T00:00:00Z","timestamp":1756166400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2021-IP17"},{"name":"2020-IP16"},{"name":"2019-IP5"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Background\/Objectives: Gestational diabetes (GD) is a common pregnancy complication linked to inflammation. Obesity, a major risk factor, is associated with elevated pro-inflammatory markers (TNF-\u03b1, IL-6) and reduced anti-inflammatory IL-10 and adiponectin. This study investigated the role of inflammatory factors (IL-6, TNF-\u03b1, IL-10, adiponectin) and their genetic variants (rs1800629, rs1800796, rs1800896, rs266729) in a unique four-group study design of pregnant women. Methods: We collected venous blood from 162 women in the third trimester of pregnancy. We measured IL-6, IL-10, TNF-\u03b1, and adiponectin levels and performed real-time PCR genotyping for the selected SNPs. Results: IL-6 levels were significantly higher (p &lt; 0.001) in pregnant women with GD and additional complications. The IL-6 SNP rs1800796 heterozygous CG genotype showed a slightly increased GD risk (OR = 1.41). However, we found no significant associations between GD and TNF-\u03b1 rs1800629 or IL-10 rs1800896 SNPs. The AdipoQ rs266729 homozygous CC genotype was linked to increased GD risk (p = 0.03 for superdominant model). Importantly, no significant correlations were observed between inflammatory marker levels and gene variants within any study group. Conclusions: Our findings suggest a greater inflammatory burden in GD pregnancies with additional complications. While certain IL-6 and AdipoQ variants might contribute to GD risk, the overall weak association between inflammatory markers and gene variants likely reflects the complex polygenic nature of GD, environmental factors, or the study\u2019s sample size.<\/jats:p>","DOI":"10.3390\/diagnostics15172153","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T10:35:17Z","timestamp":1756204517000},"page":"2153","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Inflammatory Markers and Genetic Variants in Gestational Diabetes and Pregnancy Complications: A Cross-Sectional Study"],"prefix":"10.3390","volume":"15","author":[{"given":"Jelena","family":"Omazi\u0107","sequence":"first","affiliation":[{"name":"Department of Laboratory Diagnostic, \u201cDr. Juraj Njavro\u201d National Memorial Hospital, 32000 Vukovar, Croatia"},{"name":"Department of Medical Chemistry, Biochemistry and Clinical Chemistry, Faculty of Medicine, Josip Juraj Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3245-8318","authenticated-orcid":false,"given":"Andrijana","family":"Muller","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, University Hospital Center Osijek, 31000 Osijek, Croatia"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Josip Juraj Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3005-4571","authenticated-orcid":false,"given":"Mirta","family":"Kadivnik","sequence":"additional","affiliation":[{"name":"Clinic of Obstetrics and Gynecology, University Hospital Center Osijek, 31000 Osijek, Croatia"},{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Josip Juraj Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4481-6365","authenticated-orcid":false,"given":"Kristina","family":"Kralik","sequence":"additional","affiliation":[{"name":"Department of Medical Statistics and Informatics, Faculty of Medicine, Josip Juraj Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0621-5403","authenticated-orcid":false,"given":"Domagoj","family":"Vidosavljevi\u0107","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Faculty of Medicine, Josip Juraj Strossmayer University, 31000 Osijek, Croatia"},{"name":"Department of Obstetrics and Gynecology, \u201cDr. Juraj Njavro\u201d National Memorial Hospital, 32000 Vukovar, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1126-7523","authenticated-orcid":false,"given":"Jasenka","family":"Wagner","sequence":"additional","affiliation":[{"name":"Department of Medical Biology and Genetics, Faculty of Medicine, Josip Juraj Strossmayer University, 31000 Osijek, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1524","DOI":"10.4239\/wjd.v14.i10.1524","article-title":"Effect of individualized nutrition interventions on clinical outcomes of pregnant women with gestational diabetes mellitus","volume":"14","author":"Luo","year":"2023","journal-title":"World J. Diabetes"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Omazi\u0107, J., Muller, A., Duman\u010di\u0107, B., Kadivnik, M., Aladrovi\u0107, J., Pa\u0111en, L., Krilik, K., Brki\u0107, N., Dobro\u0161evi\u0107, B., and Vukovi\u0107, B. (2024). Metabolic and Immune Parameters in Pregnant Women with Impaired Glucose Metabolism\u2014A Pilot Study. Metabolites, 14.","DOI":"10.3390\/metabo14100551"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"de Mendon\u00e7a, E.L.S.S., Fragoso, M.B.T., de Oliveira, J.M., Xavier, J.A., Goulart, M.O.F., and de Oliveira, A.C.M. (2022). Gestational Diabetes Mellitus: The Crosslink among Inflammation, Nitroxidative Stress, Intestinal Microbiota and Alternative Therapies. Antioxidants, 11.","DOI":"10.3390\/antiox11010129"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Khambule, L., and George, J.A. (2019). The Role of Inflammation in the Development of GDM and the Use of Markers of Inflammation in GDM Screening. Reviews on Biomarker Studies of Metabolic and Metabolism-Related Disorders, Springer International Publishing.","DOI":"10.1007\/978-3-030-12668-1_12"},{"key":"ref_5","first-page":"41","article-title":"Effect of tumor necrosis factor-alpha on endometrial glucose transporter-4 expression in patients with polycystic ovary syndrome through nuclear factor-kappaB signaling pathway activation","volume":"72","author":"Ha","year":"2021","journal-title":"J. Physiol. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1093\/molehr\/gah069","article-title":"The cytokine receptor gp130 and its soluble form are under hormonal control in human endometrium and decidua","volume":"10","author":"Heinrich","year":"2004","journal-title":"Mol. Hum. Reprod."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Omazi\u0107, J., Viljeti\u0107, B., Ivi\u0107, V., Kadivnik, M., Zibar, L., M\u00fcller, A., and Wagner, J. (2021). Early markers of gestational diabetes mellitus: What we know and which way forward?. Biochem. Medica, 31.","DOI":"10.11613\/BM.2021.030502"},{"key":"ref_8","first-page":"230742","article-title":"Interleukin 10 and Tumor Necrosis Factor-Alpha in Pregnancy: Aspects of Interest in Clinical Obstetrics","volume":"2012","author":"Vernini","year":"2012","journal-title":"Int. Sch. Res. Not."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1111\/j.1600-0897.2010.00810.x","article-title":"REVIEW ARTICLE: Interleukin-10: A Multi-Faceted Agent of Pregnancy","volume":"63","author":"Thaxton","year":"2010","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1186\/s13098-020-00582-8","article-title":"Whether the risk of gestational diabetes mellitus is affected by TNF-\u03b1, IL-6, IL-10 or ADIPOQ polymorphisms: A meta-analysis","volume":"12","author":"Huang","year":"2020","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1089\/gtmb.2020.0069","article-title":"Association of Single Nucleotide Polymorphisms of the IL-6, IL-10, and TNF-\u03b1 Genes with Susceptibility to Gestational Diabetes Mellitus","volume":"24","author":"Wei","year":"2020","journal-title":"Genet. Test. Mol. Biomark."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1080\/09513590.2020.1804549","article-title":"Association between TNF-\u03b1 polymorphisms and gestational diabetes mellitus: A meta-analysis and trial sequential analysis","volume":"37","author":"Liu","year":"2021","journal-title":"Gynecol. Endocrinol. Off. J. Int. Soc. Gynecol. Endocrinol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s13098-022-00851-8","article-title":"IL-6 gene rs1800795 polymorphism and diabetes mellitus: A comprehensive analysis involving 42,150 participants from a meta-analysis","volume":"14","author":"Cheng","year":"2022","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Obirikorang, C., Lokpo, S.Y., Owiredu, W.K.B.A., Ahenkorah-Fondjo, L., Osei-Yeboah, J., Duedu, K.O., Adejumo, E.N., Ametepe, S., Asamoah, E.A., and Coffie, S.A. (2024). Association between Interleukin-6 Gene Polymorphism (rs1800795 and rs1800796) and Type 2 Diabetes Mellitus in a Ghanaian Population: A Case-Control Study in the Ho Municipality. BioMed Res. Int., 2024.","DOI":"10.1155\/2024\/3610879"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"144302","DOI":"10.1016\/j.gene.2019.144302","article-title":"The roles of ADIPOQ rs266729 and MTNR1B rs10830963 polymorphisms in patients with gestational diabetes mellitus: A meta-analysis","volume":"730","author":"Bai","year":"2020","journal-title":"Gene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1007\/s00404-013-3029-z","article-title":"The rs266729 single-nucleotide polymorphism in the adiponectin gene shows association with gestational diabetes","volume":"289","author":"Beltcheva","year":"2014","journal-title":"Arch. Gynecol. Obstet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.gene.2015.06.004","article-title":"Association of adiponectin gene polymorphism rs266729 with type two diabetes mellitus in Iraqi population. A pilot study","volume":"570","author":"Kaftan","year":"2015","journal-title":"Gene"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e8745","DOI":"10.1097\/MD.0000000000008745","article-title":"The polymorphism of rs266729 in adiponectin gene and type 2 diabetes mellitus: A Meta-Analysis","volume":"96","author":"Sun","year":"2017","journal-title":"Medicine"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1111\/j.1365-2125.2004.02103.x","article-title":"The revision of the Declaration of Helsinki: Past, present and future","volume":"57","author":"Carlson","year":"2004","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"e98","DOI":"10.2337\/dc10-0719","article-title":"International association of diabetes and pregnancy study groups recommendations on the diagnosis and classification of hyperglycemia in pregnancy","volume":"33","author":"Metzger","year":"2010","journal-title":"Diabetes Care"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.5468\/ogs.20020","article-title":"Role of interleukin-6 (IL-6) in predicting gestational diabetes mellitus","volume":"63","author":"Amirian","year":"2020","journal-title":"Obstet. Gynecol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1016\/S0140-6736(05)67424-7","article-title":"Genetic association studies","volume":"366","author":"Clayton","year":"2005","journal-title":"Lancet"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1038\/nprot.2010.182","article-title":"Basic statistical analysis in genetic case-control studies","volume":"6","author":"Clarke","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.diabres.2018.01.023","article-title":"Interleukin-10-1082A>G (rs1800896) polymorphism is associated with diabetic retinopathy in type 2 diabetes","volume":"138","author":"Polina","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Omazi\u0107, J., Muller, A., Kadivnik, M., Dobro\u0161evi\u0107, B., Vukovi\u0107, B., Florijan\u010di\u0107, M., and Wagner, J. (2025). Comparative Assessment of Immune Cell Subset Ratios (NKT\/NK, Th\/Tc, B1\/B2) in Gestational Diabetes and Healthy Pregnancy: Links to Biochemical and Immunochemical Profiles. Metabolites, 15.","DOI":"10.3390\/metabo15060378"}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/17\/2153\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T18:32:54Z","timestamp":1760034774000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/15\/17\/2153"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,26]]},"references-count":25,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2025,9]]}},"alternative-id":["diagnostics15172153"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics15172153","relation":{},"ISSN":["2075-4418"],"issn-type":[{"value":"2075-4418","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,26]]}}}