{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:22:41Z","timestamp":1760487761478,"version":"build-2065373602"},"reference-count":12,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:00:00Z","timestamp":1760400000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Immune thrombocytopenia (ITP) is a common pediatric autoimmune disorder characterized by low platelet counts and heightened bleeding risk. Fc gamma receptors (Fc\u03b3Rs), particularly <jats:italic>FCGR2A<\/jats:italic> (131H\/R) and <jats:italic>FCGR3A<\/jats:italic> (158F\/V), mediate immune responses and may influence ITP susceptibility and progression. Gender-related genetic variation has been proposed but remains underexplored, particularly in Middle Eastern pediatric populations. This study aimed to perform an exploratory assessment of the prevalence and potential clinical relevance of <jats:italic>FCGR2A<\/jats:italic> and <jats:italic>FCGR3A<\/jats:italic> polymorphisms, including gender-based tendencies, in Palestinian children with ITP.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A multicenter case-control study included 40 proven pediatric ITP patients (20 males, 20 females; mean age 6.76 \u00b1 4.13 years) and 80 age- and sex-matched healthy controls. Genotyping was performed using PCR-RFLP and nested PCR. Genotype frequencies were correlated with disease phenotype and sex.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>No statistically significant differences in genotype distributions were observed between ITP cases and controls for either <jats:italic>FCGR2A<\/jats:italic> (HH: 17.5%, HR: 62.5%, RR: 20.0%) or <jats:italic>FCGR3A<\/jats:italic> (FF: 25.0%, FV: 55.0%, VV: 20.0%) (<jats:italic>p<\/jats:italic> &amp;gt; 0.05). However, a secondary, exploratory analysis for gender-specific trends yielded noteworthy observations: <jats:italic>FCGR2A<\/jats:italic>-HH was numerically more frequent in male ITP patients (57.4%) than in females (42.8%), while HR was lower in males (48% vs. 52%). Similarly, <jats:italic>FCGR3A<\/jats:italic>-VV occurred in 62.5% of male ITP patients versus 37.5% in females. Furthermore, the combined <jats:italic>HR\/FV<\/jats:italic> genotype (32.5%) showed a non-significant trend of association with chronic ITP (69.2%), while the <jats:italic>VV\/HH<\/jats:italic> genotype, although rare (5%), was linked to 50% of refractory presentations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This exploratory study found no statistically significant association between <jats:italic>FCGR2A<\/jats:italic> and <jats:italic>FCGR3A<\/jats:italic> polymorphisms and overall ITP susceptibility in the full cohort. However, the observed trends, particularly the distinct gender-based distribution of specific genotypes and the association of combined genotypes with chronic and refractory disease, suggest that these genetic markers may play a role in disease progression. Further investigation in a larger, appropriately powered study is warranted to validate these findings and to understand their potential to guide personalized treatment approaches for pediatric ITP.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1606953","type":"journal-article","created":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:25:59Z","timestamp":1760419559000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Combined FCGR2A (131H\/R) and FCGR3A (158F\/V) genotypes and their gender-specific association with chronic and refractory immune thrombocytopenia in Palestinian children"],"prefix":"10.3389","volume":"12","author":[{"given":"Khitam","family":"Amer","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johnny","family":"Amer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adham Abu","family":"Taha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wisam","family":"Baker","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Awad","family":"Abuhamed","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahmad","family":"Salhab","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"776","DOI":"10.1056\/NEJMra2010141","article-title":"Immune thrombocytopenia.","volume":"385","author":"Cines","year":"2021","journal-title":"N Engl J Med."},{"key":"B2","first-page":"100635","article-title":"The management of immune thrombocytopenia: current approaches and emerging therapies.","volume":"41","author":"Kuter","year":"2020","journal-title":"Blood Rev."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2800","DOI":"10.1182\/bloodadvances.2019000368","article-title":"International consensus report on the investigation and management of primary immune thrombocytopenia.","volume":"3","author":"Provan","year":"2019","journal-title":"Blood Adv."},{"key":"B4","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1080\/10245332.2020.1715098","article-title":"Fc\u03b3 receptor polymorphisms and their association with immune thrombocytopenia: a systematic review and meta-analysis.","volume":"25","author":"Liu","year":"2020","journal-title":"Hematology."},{"key":"B5","doi-asserted-by":"publisher","first-page":"102752","DOI":"10.1016\/j.jaut.2022.102752","article-title":"The impact of Fc\u03b3 receptor polymorphisms on autoimmune disease susceptibility: a comprehensive review.","volume":"124","author":"Zhang","year":"2022","journal-title":"J Autoimmunity."},{"key":"B6","first-page":"145","article-title":"Fc gamma receptor polymorphisms and therapeutic response in immune thrombocytopenia.","volume":"15","author":"Garcia-Sanchez","year":"2021","journal-title":"Hematol Rev."},{"key":"B7","first-page":"50","article-title":"Current advances in the understanding of Fc\u03b3 receptor polymorphisms in autoimmune disorders.","volume":"16","author":"Park","year":"2023","journal-title":"J Hematol Oncol."},{"key":"B8","doi-asserted-by":"publisher","first-page":"389","DOI":"10.1016\/j.ejmhg.2013.08.006","article-title":"The role of immune system gene polymorphisms in Egyptian children with immune thrombocytopenia.","volume":"14","author":"Elalfy","year":"2013","journal-title":"Egyptian J Med Hum Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"754","DOI":"10.1182\/blood.V99.3.754","article-title":"Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG Fc receptor Fc\u03b3RIIIa gene.","volume":"99","author":"Cartron","year":"2002","journal-title":"Blood."},{"key":"B10","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1097\/MBC.0b013e32834bf726","article-title":"FcgammaRIIIa genetic polymorphism in Egyptian pediatric patients with chronic primary immune thrombocytopenia.","volume":"23","author":"Eyada","year":"2012","journal-title":"Blood Coagulation Fibrinolysis."},{"key":"B11","doi-asserted-by":"publisher","first-page":"710","DOI":"10.1002\/pbc.2435","article-title":"FcgammaRIIa and FcgammaRIIIa polymorphisms and childhood immune thrombocytopenic purpura.","volume":"60","author":"Papagianni","year":"2013","journal-title":"Pediatric Blood Cancer."},{"key":"B12","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1080\/08880018.2018.152615","article-title":"Fc\u03b3 receptor polymorphisms in pediatric immune thrombocytopenia: a single-center experience.","volume":"35","author":"Pavkovic","year":"2018","journal-title":"Pediatr Hematol Oncol."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1606953\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:26:00Z","timestamp":1760419560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2025.1606953\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,14]]},"references-count":12,"alternative-id":["10.3389\/fmed.2025.1606953"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2025.1606953","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,14]]},"article-number":"1606953"}}