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As retinopathy of prematurity (ROP) is a neurovascular retinal disease, this study analyzed the contributions of NGF (rs6330), BDNF (rs7934165), TH (rs10770141), and EPO (rs507392) genetic functional polymorphisms to the modulation of hematological and biochemical parameters of the first week of life and their association with ROP development. A multicenter cohort of 396 preterm infants (gestational age &lt; 32 weeks or birth weight &lt; 1500 g) was genotyped using MicroChip DNA and iPlex MassARRAY\u00ae platform. Multivariate regression followed univariate assessment of ROP risk factors. NGF (GG) genotype was associated with a higher ROP risk (OR = 1.79), which increased further (OR = 2.38) when epistatic interactions with TH (allele C) and BDNF (allele G) were present. Significant circulating biomarker differences, including bilirubin, erythrocytes, monocytes, neutrophils, lymphocytes, and platelet markers, were found between ROP and non-ROP groups, with variations depending on the polymorphism. These findings suggest that NGF (rs6330) and its interactions with related genes contribute to ROP risk, providing valuable insights into the genetic and biological mechanisms underlying the disease and identifying potential predictive biomarkers.<\/jats:p>","DOI":"10.3390\/ijms26030898","type":"journal-article","created":{"date-parts":[[2025,1,22]],"date-time":"2025-01-22T07:55:32Z","timestamp":1737532532000},"page":"898","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Influence of Functional Variations in Genes of Neurotrophins and Neurotransmitter Systems on the Development of Retinopathy of Prematurity"],"prefix":"10.3390","volume":"26","author":[{"given":"Mariza","family":"Fevereiro-Martins","sequence":"first","affiliation":[{"name":"Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"},{"name":"Grupo Ecogen\u00e9tica e Sa\u00fade Humana, Instituto de Sa\u00fade Ambiental-ISAMB, Laborat\u00f3rio Associado Terra, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o Cient\u00edfica Bento da Rocha Cabral, Cal\u00e7ada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal"},{"name":"Departamento de Oftalmologia, Hospital Cuf Descobertas, Rua M\u00e1rio Botas, 1998-018 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3688-4648","authenticated-orcid":false,"given":"Ana Carolina","family":"Santos","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"},{"name":"Grupo Ecogen\u00e9tica e Sa\u00fade Humana, Instituto de Sa\u00fade Ambiental-ISAMB, Laborat\u00f3rio Associado Terra, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"}]},{"given":"Carlos","family":"Marques-Neves","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"},{"name":"Grupo Ecogen\u00e9tica e Sa\u00fade Humana, Instituto de Sa\u00fade Ambiental-ISAMB, Laborat\u00f3rio Associado Terra, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"},{"name":"Centro de Estudos das Ci\u00eancias da Vis\u00e3o, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, Piso 1C, 1649-028 Lisboa, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6402-3285","authenticated-orcid":false,"given":"Herc\u00edlia","family":"Guimar\u00e3es","sequence":"additional","affiliation":[{"name":"Departamento de Ginecologia-Obstetr\u00edcia e Pediatria, Faculdade de Medicina, Universidade do Porto, Alameda Prof. Hern\u00e2ni Monteiro, 4200-319 Porto, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5773-5687","authenticated-orcid":false,"given":"Manuel","family":"Bicho","sequence":"additional","affiliation":[{"name":"Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"},{"name":"Grupo Ecogen\u00e9tica e Sa\u00fade Humana, Instituto de Sa\u00fade Ambiental-ISAMB, Laborat\u00f3rio Associado Terra, Faculdade de Medicina, Universidade de Lisboa, Av. Professor Egas Moniz, 1649-028 Lisboa, Portugal"},{"name":"Instituto de Investiga\u00e7\u00e3o Cient\u00edfica Bento da Rocha Cabral, Cal\u00e7ada Bento da Rocha Cabral 14, 1250-012 Lisboa, Portugal"}]},{"name":"on behalf of the GenE-ROP Study Group","sequence":"additional","affiliation":[]}],"member":"1968","published-online":{"date-parts":[[2025,1,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ajo.2021.07.016","article-title":"Retinopathy of Prematurity: Advances in the Screening and Treatment of Retinopathy of Prematurity Using a Single Center Approach HHS Public Access","volume":"33136","author":"Berrocal","year":"2022","journal-title":"Am. J. 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