Identification of ACOT13 and PTGER2 as novel candidate genes of autosomal dominant polycystic kidney disease through whole exome sequencing

European Journal of Medical Research

Dan Dong¹  Yong Liu²  Xiaohua Li³  Lihe Che³  Luyao Sun³  Na Du³  Bin Wang³ 

[1] Department of Obstetrics and Gynecology, The First Hospital of Jilin University, No.1 Xinmin Street, 130021, Changchun, Jilin, China;Genetic Diagnosis Center, The First Hospital of Jilin University, No.1 Xinmin Street, 130021, Changchun, Jilin, China;Infectious Diseases Department, The First Hospital of Jilin University, No.1 Xinmin Street, 130021, Changchun, Jilin, China;

关键词: Whole exome sequencing;    Gene mutations;    Polycystic kidney disease;    ACOT13;    PTGER2;   

DOI  :  10.1186/s40001-021-00613-8

来源: Springer

【 摘 要 】

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder. Half of the patients would slowly progress to end-stage renal disease. However, the potential target for ADPKD treatment is still lacking.MethodsFour ADPKD patients and two healthy family members were included in this study. The peripheral blood samples were obtained and tested by the whole exome sequencing (WES). The autosomal mutations in ADPKD patients were retained as candidate sites. The Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein–protein interaction network (PPI) analyses were performed by clusterProfiler R package. A dataset containing 18 ADPKD patients and three normal samples were downloaded from the Gene Expression Omnibus (GEO) database and analyzed using the limma R package.ResultsA total of six mutant genes were identified based on the dominant genetic pattern and most of them had not been reported to be associated with ADPKD. Furthermore, 19 harmful genes were selected according to the harmfulness of mutation. GO and KEGG enrichment analyses showed that the processes of single-organism cellular process, response to stimulus, plasma membrane, cell periphery, and anion binding as well as cyclic adenosine monophosphate (cAMP) signaling pathway and pathways in cancer were significantly enriched. Through integrating PPI and gene expression analyses, acyl-CoA thioesterase 13 (ACOT13), which has not been reported to be related to ADPKD, and prostaglandin E receptor 2 (PTGER2) were identified as potential genes associated with ADPKD.ConclusionsThrough combination of WES, gene expression, and PPI network analyses, we identified ACOT13 and PTGER2 as potential ADPKD-related genes.

【 授权许可】

CC BY