{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T05:25:34Z","timestamp":1766035534057,"version":"3.48.0"},"reference-count":67,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Early-onset inflammatory bowel disease (IBD), including Crohn\u2019s disease (CD) and ulcerative colitis (UC), frequently presents with a more severe clinical course. Genetic susceptibility, particularly involving the TGF-\u03b2 signaling pathway, plays a key role in IBD pathogenesis. SMAD3 and LTBP3 encode crucial components of this pathway and have been implicated in IBD in previous genome-wide association studies. Methods: This study aimed to assess the clinical significance of the rs17293632 (SMAD3) and rs11545200 (LTBP3) polymorphisms in a pediatric IBD cohort. A total of 286 children (133 with UC and 153 with CD) were recruited from seven pediatric centers in Poland. Clinical data included age at diagnosis, inflammatory markers (CRP, albumin), growth indices (Z-scores for weight, height, and BMI), and treatment regimens. Results: The LTBP3 rs11545200 minor allele was significantly associated with a younger age at diagnosis, poorer nutritional status during disease flares, and a more frequent use of infliximab\u2014particularly in patients with UC. In CD, the SMAD3 rs17293632 major homozygous genotype was associated with increased use of systemic corticosteroids, suggesting a more severe or treatment-resistant disease phenotype. Conclusions: The assessed polymorphisms in LTBP3 and SMAD3, both involved in TGF-\u03b2 signaling, are associated with clinical characteristics of pediatric IBD. These findings support the potential role of genetic variants as biomarkers for disease severity and treatment tailoring, contributing to the development of personalised therapeutic strategies in children with IBD.<\/jats:p>","DOI":"10.3390\/genes16121511","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T17:22:58Z","timestamp":1765905778000},"page":"1511","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["From Polymorphisms to Phenotypes: SMAD3 rs17293632 and LTBP3 rs11545200 in Pediatric Inflammatory Bowel Disease"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1398-3387","authenticated-orcid":false,"given":"Jan","family":"Brylak","sequence":"first","affiliation":[{"name":"Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariusz","family":"Szczepanik","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0953-2188","authenticated-orcid":false,"given":"Jan K.","family":"Nowak","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0257-6180","authenticated-orcid":false,"given":"Ma\u0142gorzata","family":"Jamka","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3017-0524","authenticated-orcid":false,"given":"Aleksandra","family":"Glapa-Nowak","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aleksandra","family":"Banaszkiewicz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrzej","family":"Radzikowski","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Nutrition, Medical University of Warsaw, 02-091 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anna","family":"Szaflarska-Pop\u0142awska","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endoscopy and Gastrointestinal Function Testing, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, 85-094 Bydgoszcz, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6764-8261","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Kwiecie\u0144","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urszula","family":"Grzybowska-Chlebowczyk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Faculty of Medical Sciences in Katowice, Medical University of Silesia, 40-055 Katowice, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edyta","family":"Kawa\u0142kowska","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5248-1246","authenticated-orcid":false,"given":"Anna","family":"Wiernicka","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, The Children\u2019s Memorial Health Institute, 04-730 Warsaw, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5813-5707","authenticated-orcid":false,"given":"Jaros\u0142aw","family":"Walkowiak","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology and Metabolic Diseases, Poznan University of Medical Sciences, 60-572 Poznan, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","unstructured":"Malik, T.F., and Aurelio, D.M. 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