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

Na Du,Dan Dong,Bin Wang,Lihe Che,Xiaohua Li,Luyao Sun,Yong Liu

doi:10.1186/s40001-021-00613-8

Abstract

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.

Highlights

Polycystic kidney disease (PKD) is a group of monogenic disorders, and is the common cause of end-stage renal disease
Through integrated analyses of gene mutation, gene expression, gene function enrichment, and protein–protein interaction (PPI), we identified two genes (ACOT13 and prostaglandin E receptor 2 (PTGER2)) which were potentially associated with the pathogenesis of Autosomal dominant polycystic kidney disease (ADPKD)
19 genes were selected according to the harmfulness of mutation, including MUTYH, USH2A, HBS1L, GLI3, SBDS, SND1, ABCA2, RPS6KA4, FLVCR1, ATIC, SCN11A, ATP6V1A, GLRA1, PRMT8, PKD1, INSL3, SUPT5H, NCF4, and GPR143

Summary

Introduction

Polycystic kidney disease (PKD) is a group of monogenic disorders, and is the common cause of end-stage renal disease. Most adult patients are affected by the autosomal dominant form (ADPKD), while the autosomal recessive polycystic kidney disease (ARPKD) is a rarer form that usually presents perinatally or in early childhood [1]. 1 and 2 (PC1 and PC2) proteins, are the most common causes of ADPKD. PKD is inherited monogenically, it is heterogeneous in phenotype, gene, and allele [1], and 7% of ADPKD families are genetically unresolved [5]. The molecular mechanisms underlying the renal dysfunction resulted from mutations in PKD genes and the physiological functions of polycystin proteins are still unclear [6]. Autosomal dominant polycystic kidney disease (ADPKD) is the most common monogenic kidney disorder. The potential target for ADPKD treatment is still lacking

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Results

Conclusion