Choręziak-Michalak Aneta, Szpecht Dawid, Woźniak Tomasz, Chmielarz-Czarnocińska Anna, Gazińska Patrycja, Gotz-Więckowska Anna, Strauss Ewa
Chair and Department of Ophthalmology, Poznan University of Medical Sciences, Poznan, Poland.
Chair and Department of Neonatology, Poznan University of Medical Sciences, Poznan, Poland.
Sci Rep. 2025 Jan 2;15(1):329. doi: 10.1038/s41598-024-83305-7.
Despite advances in neonatal and ophthalmological care, retinopathy of prematurity (ROP) continues to be a leading cause of childhood blindness worldwide. Investigating gene variants associated with vascular responses in ROP may provide valuable insights into its pathogenesis and identify risk or protective factors. Nitric oxide (NO) and endothelin-1 (ET-1) play roles in vascular regulation, influencing processes relevant to ROP development. Functional variants of genes encoding endothelial NO sythetase (NOS3 rs1799983, rs2070744), endothelin-1 (EDN1 rs5370), and endothelin receptor A (EDNRA rs5335) may influence ROP development or progression. The results of our study support the role of the rs2070744 variant in ROP. We identified the protective effect of the rs2070744C allele against the development of ROP requiring treatment, also after adjusting for covariates. Meta-analysis including 298 patients and 397 controls confirmed this protective role. The rs2070744CC homozygous genotype exhibited an odds ratio (OR) of 0.42 (adjusted P = 0.036). Additional meta-analysis results for NOS3 rs1799983 are presented, suggesting potential risk in a recessive model. No associations were found between EDN1, EDNRA variants, and ROP. Exploring genetic predispositions in ROP, including vascular regulation genes, can lead to personalized prevention and treatment approaches. Our results need to be replicated in a larger sample of premature infants.
尽管新生儿和眼科护理取得了进展，但早产儿视网膜病变（ROP）仍然是全球儿童失明的主要原因。研究与ROP血管反应相关的基因变异可能为其发病机制提供有价值的见解，并识别风险或保护因素。一氧化氮（NO）和内皮素-1（ET-1）在血管调节中起作用，影响与ROP发展相关的过程。编码内皮型一氧化氮合酶（NOS3 rs1799983、rs2070744）、内皮素-1（EDN1 rs5370）和内皮素受体A（EDNRA rs5335）的基因功能变异可能影响ROP的发展或进展。我们的研究结果支持rs2070744变异在ROP中的作用。我们确定了rs2070744C等位基因对需要治疗的ROP发展的保护作用，在调整协变量后也是如此。纳入298例患者和397例对照的荟萃分析证实了这一保护作用。rs2070744CC纯合基因型的优势比（OR）为0.42（校正P = 0.036）。还给出了NOS3 rs1799983的其他荟萃分析结果，提示在隐性模型中有潜在风险。未发现EDN1、EDNRA变异与ROP之间存在关联。探索ROP的遗传易感性，包括血管调节基因，可导致个性化的预防和治疗方法。我们的结果需要在更大样本的早产儿中进行重复验证。
