AUTHOR=Song Qiaoling , Zhang Yuchao , Zhang Minghui , Ma Xiaoli , Zhang Qianyue , Zhao Chenyang , Zhang Zhongwen , Zhao Huichen , Hu Wenchao , Zhang Xinxin , Ren Xiwen , An Ming , Yang Jinbo , Liu Yuantao TITLE=Identifying gene variants underlying the pathogenesis of diabetic retinopathy based on integrated genomic and transcriptomic analysis of clinical extreme phenotypes JOURNAL=Frontiers in Genetics VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2022.929049 DOI=10.3389/fgene.2022.929049 ISSN=1664-8021 ABSTRACT=

Diabetic retinopathy (DR) is a common complication and the leading cause of blindness in patients with type 2 diabetes. DR has been shown to be closely correlated with blood glucose levels and the duration of diabetes. However, the onset and progression of DR also display clinical heterogeneity. We applied whole-exome sequencing and RNA-seq approaches to study the gene mutation and transcription profiles in three groups of diabetic patients with extreme clinical phenotypes in DR onset, timing, and disease progression, aiming to identify genetic variants that may play roles in the pathogenesis of DR. We identified 23 putatively pathogenic genes, and ingenuity pathway analysis of these mutated genes reveals their functional association with glucose metabolism, diabetic complications, neural system activity, and dysregulated immune responses. In addition, ten potentially protective genes were also proposed. These findings shed light on the mechanisms underlying the pathogenesis of DR and may provide potential targets for developing new strategies to combat DR.