Osteomodulin is a Potential Genetic Target for Hypertrophic Cardiomyopathy.

Wenjie Guo, Weijing Feng, Xianglin Fan, Jing Huang, Caiwen Ou, Minsheng Chen

Biochemical genetics 2021 Oct

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Hypertrophic cardiomyopathy (HCM) is one of the most common genetic heart diseases. Its features include abnormal cardiomyocyte hypertrophy, microvascular dysfunction, and increased accumulation of intercellular matrix. We aim to unravel genes associated with the pathogenesis of HCM and provide a potential target for diagnosis and treatment. Key modules were identified by weighted gene co-expression network analysis (WGCNA). A miRNA-mRNA network was constructed with the predicted miRNA and the most likely hub gene was screened out for gene set enrichment analysis (GSEA). The diagnostic capacity of hub gene was verified by receiver operating characteristic (ROC) curves. Single-cell sequencing (sc-RNA seq) data of normal adult hearts were used to further predict the specific cell types expressing the hub gene. WGCNA assigned genes into different modules and found that the genes contained in the red module had the strongest positive correlation with HCM disease. 2.5% of the genes were common between DEG and hub genes. With the miRNA-mRNA network, osteomodulin (OMD) was identified as the most potential hub gene. GSEA showed that OMD was mainly involved in the synthesis of extracellular matrix and had a certain inhibitory effect on the immune system. The expression of OMD in HCM was validated and ROC curve analysis showed that OMD could distinguish HCM from controls with the area under the curve (AUC) > 0.7. The sc-RNA seq revealed that OMD was mainly expressed in the later stages of cardiac fibroblasts, suggesting that OMD may have an effect on fibroblasts, participating in the pathogenesis of HCM. OMD may serve as a biomarker and therapeutic target for HCM in the future. © 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Citation

Wenjie Guo, Weijing Feng, Xianglin Fan, Jing Huang, Caiwen Ou, Minsheng Chen. Osteomodulin is a Potential Genetic Target for Hypertrophic Cardiomyopathy. Biochemical genetics. 2021 Oct;59(5):1185-1202