Multi-omics identification of microvascular endothelium-related genes in patients with diabetic organic erectile dysfunction
10.13263/j.cnki.nja.2025.11.002
- VernacularTitle:单细胞测序鉴定糖尿病器质性勃起功能障碍患者微血管内皮相关基因
- Author:
Lijuan WU
1
;
Weizhuo WANG
;
Kang CHEN
;
Zheng TANG
;
Kai FU
;
Mingyan TANG
;
Wanglei YANG
Author Information
1. 苏州大学附属第二医院生殖医学中心,江苏苏州 215004
- Publication Type:Journal Article
- Keywords:
single-cell sequencing;
erectile dysfunction;
Mendelian randomization;
biomarker
- From:
National Journal of Andrology
2025;31(11):972-978
- CountryChina
- Language:Chinese
-
Abstract:
Objective To integrate patient clinical information with single-cell sequencing analysis to identify key genes involved in organic erectile dysfunction(ED)in diabetic patients,and to further validate these findings using genome-wide association study(GWAS)data to pinpoint the genes associated with diabetic organic ED.Methods Single-cell RNA sequen-cing data were downloaded from the GSE206528 dataset,comprising samples from five patients including three individuals with-out ED or diabetes,and two patients diagnosed with diabetic ED.Data preprocessing,cell clustering,and annotation were per-formed using R,followed by extraction of microvascular endothelial cells for differential expression analysis.Enrichment analysis of the identified differentially expressed genes(DEGs)was conducted using the Hiplot platform.Expression quantitative trait loci(eQTL)single nucleotide polymorphisms(SNPs)corresponding to these DEGs were retrieved from the UK Biobank(UKB)da-tabase as exposures.ED(GWAS ID:ebi-a-GCST006956)was defined as the outcome variable.Mendelian randomization(MR)analysis was then performed to identify potential causal genes.Results Using the Seurat package,single-cell RNA se-quencing data from the five patients underwent quality control and integration.After cell type identification,a subset of microvas-cular endothelial cells was selected for differential expression analysis,resulting in the identification of 214 DEGs.Functional enrichment analysis revealed that these genes were significantly enriched in pathways related to diabetic complications,including the AGE-RAGE signaling pathway,TNF signaling pathway,and oxidative phosphorylation.Subsequently,MR analysis was per-formed on the 214 DEGs,using erectile dysfunction(ebi-a-GCST006956)as the outcome.Six genes were identified as potential causal genes including MYL9,NFIB,ENDOD1,DES,NRARP and HSPA1B.Conclusion These findings suggest that MYL9,NFIB,ENDOD1,DES,NRARP and HSPA1B may play a role in the progression of organic ED in diabetic patients.
