# Mechanism of action and experimental validation of key genes common to diabetic retinopathy and coronary heart disease based on multiple bioinformatics investigations

## TL;DR

This study identifies HIRIP3 and ZNF416 as key genes linking diabetic retinopathy and coronary heart disease, offering potential new treatment targets.

## Contribution

The study identifies novel key genes (HIRIP3 and ZNF416) and their immune cell correlations in diabetic retinopathy and coronary heart disease.

## Key findings

- HIRIP3 and ZNF416 show consistent expression trends across multiple datasets and correlate with specific immune cells.
- ZNF416 is significantly upregulated in control groups compared to DR with CHD groups.
- Potential drugs targeting these genes were identified with stable binding conformations.

## Abstract

The relationship between diabetic retinopathy (DR) and coronary artery disease (CHD) has been established as a reliable predictor. However, the underlying mechanisms linking these two conditions remain poorly understood. Identifying common key genes could provide new therapeutic targets for both diseases.

Public databases were used to compile training and validation datasets for DR and CHD. Machine learning algorithms and expression validation were employed to identify these key genes. To investigate immune cell differences, single-sample gene set enrichment analysis (ssGSEA) and the Wilcoxon test were applied. Spearman correlation analysis further explored the relationship between key genes and immune cell variations. Additionally, potential therapeutic drugs targeting these key genes were identified and a key gene–drug network was constructed. The role of the key genes in the pathogenesis of DR and CHD was further examined through reverse transcription-quantitative polymerase chain reaction (RT-qPCR).

Consistent expression trends observed across datasets (GSE221521, GSE113079, GSE189005, GSE42148) led to the identification of HIRIP3 and ZNF416 as key genes. In GSE221521, HIRIP3 was positively correlated with CD56 bright natural killer cells (cor = 0.329, P < 0.001) and type 1T helper cells (cor = 0.327, P < 0.001), while ZNF416 showed significant correlations with CD4 T cell activation (cor = 0.340, P < 0.001) and type 1T helper cells (cor = 0.273, P < 0.05). Moreover, 82 transcription factors (TFs) were predicted, including SP3. Binding free energy calculations for key genes and potential drugs suggested stable binding conformations. RT-qPCR results revealed elevated expression of both HIRIP3 and ZNF416 in the control group compared to the DR with CHD (DRwCHD) group, with only ZNF416 showing significant differences between the groups (p < 0.05).

These findings highlight HIRIP3 and ZNF416 as crucial genes in DR and CHD detection, providing a foundation for identifying novel therapeutic targets for both diseases.