Sun Huiqing, Xia Zhiyi, Li Mingchao, Yu Zengyuan, Wang Zhangsheng, Xing Shan, Cheng Ping, Zhang Hongbo, Li Lifeng
Department of Neonatology, Children's Hospital affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.
Key Laboratories of Children's Genetic Metabolic Diseases, Henan Province, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou, China.
Mol Vis. 2025 Mar 1;31:33-43. eCollection 2025.
Retinopathy of prematurity (ROP) is a pathological condition characterized by abnormal proliferation of retinal vessels and it represents the primary cause of visual impairment in preterm infants. There is increasing backing for the involvement of genetic factors in the onset of ROP.
A prospective cohort study assessed the allele frequency and genotype distribution of gene polymorphisms in angiogenesis, inflammation and oxygen-sensing pathways in preterm infants with severe ROP. The role of genetic polymorphism in ROP development was investigated using next-generation sequencing (NGS) combined with candidate genes and data mining methods.
A total of 47 confirmed severe ROP cases and gestational age, birthweight and days of oxygen therapy plus 35 similar control infants were enrolled in this study. In the initial hypothesis-generating survey, we selected a p value of 0.01 to minimize false positives while retaining true positives. Using this criterion, we identified 19 single-nucleotide polymorphisms across 11 genes that were associated with the occurrence of ROP (, , , , , , , , , and ; all p<0.001). Compared with the control group, 62 single-nucleotide polymorphisms in 19 candidate genes (, , , , , , , , , , , , , , , , , ) representing angiogenic, inflammation, oxygen-sensing pathways and proliferative retinopathic diseases were found to be associated with the development of severe ROP (all p<0.01).
Using NGS gene analysis suggests that genetic risk factors may play an important role in susceptibility to the development of ROP.
早产儿视网膜病变（ROP）是一种以视网膜血管异常增殖为特征的病理状况，是早产儿视力损害的主要原因。越来越多的证据支持遗传因素参与ROP的发病过程。
一项前瞻性队列研究评估了重度ROP早产儿血管生成、炎症和氧感应途径中基因多态性的等位基因频率和基因型分布。采用下一代测序（NGS）结合候选基因和数据挖掘方法，研究基因多态性在ROP发展中的作用。
本研究共纳入47例确诊的重度ROP病例以及胎龄、出生体重和氧疗天数，外加35例类似的对照婴儿。在最初的假设生成调查中，我们选择p值为0.01，以尽量减少假阳性，同时保留真阳性。使用该标准，我们在11个基因中鉴定出19个与ROP发生相关的单核苷酸多态性（，，，，，，，，，和；所有p<0.001）。与对照组相比，发现代表血管生成、炎症、氧感应途径和增殖性视网膜病变疾病的19个候选基因（，，，，，，，，，，，，，，，，，）中的62个单核苷酸多态性与重度ROP的发展相关（所有p<0.01）。
使用NGS基因分析表明，遗传风险因素可能在ROP发展的易感性中起重要作用。
