ABSTRACT
INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease that mainly affects the myocardium. In the current study, we aim to explore HCM-related hub genes through the analysis of differentially expressed genes (DEGs) between HCM and normal sample groups. METHODS: The GSE68316 and GSE36961 expression profiles were obtained from the Gene Expression Omnibus (GEO) database for the identification of DEGs, to explore hub genes, and to perform their expression analysis. Clinical HCM and control tissue samples were taken for expression and promoter methylation validation analysis via RNA-sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq) analyses. Then, other different bioinformatics tools were employed to perform STRING, lncRNA-miRNA-mRNA regulatory networks, gene enrichment, and drug prediction analyses. RESULTS: In total, the top 20 DEGs, including 10 up-regulated and 10 down-regulated, were obtained from GSE68316. Out of the 20 DEGs, we subsequently identified the 8 most important hub genes including 5 up-regulated genes (EPB42, UQCRH, CA1, PFDN5, and LSM5) and 3 down-regulated genes (RPS24, TNS1, and RPL26). Expression and promoter methylation dysregulation of these genes were further validated on clinical HCM samples paired with controls. Next, we further investigated hub genes' regulatory 6 miRNAs (has-mir-1-3p, has-mir-129-5p, has-mir-16-5p, has-mir-23b-3p, has-mir-27-3p, and has-mir-182-5p) and miRNAs regulatory 4 lncRNAs (NUTMB2-AS1, NEAT1, XIST, and GABPB1-AS1) in this study via the lncRNA-cricRNA-miRNA-mRNA regulatory network. Later on, gene enrichment analysis revealed that hub genes were enriched in various important pathways including Nitrogen metabolism, Ribosome, RNA degradation, Cardiac muscle contraction, and Coronavirus disease, etc. Finally, the drug prediction analysis highlighted different potential candidate drugs for altering the expression of hub genes in the treatment of HCM. CONCLUSION: In summary, the identification of key hub genes and their enrichment analysis in the current study may shed light on the mechanisms behind the occurrence and development of HCM.
ABSTRACT
Objective: To correlate the serum levels of ceruloplasmin (Cp), copper (Cu), and superoxide dismutase (SOD) with pulmonary function tests (PFTs) in non-diabetics (controls) and patients suffering from Type-1 and Type- 2 diabetes. Methods: The comparative cross-sectional study of 348 participants was performed at the Baqai Institute of Diabetes and Endocrinology (BIDE) - Karachi, Pakistan, from February 2019 to September 2020. Individuals having diabetes-related complications, asthma, chronic obstructive pulmonary disease, chest infection, pregnant women and smokers were excluded. A total of 348 participants were included into three groups after signing informed consent. The control group had 107 non-diabetic participants, with an age range of 6 to 60 years. The diagnosed T1D group (n=107) had an age range of 6 to 25 years. While diagnosed T2D group (n=134) had an age range of 26 to 60 years. During the fasting state, anthropometric parameters, blood pressure, spirometry, and a venous blood sample (5ml) were collected to measure serum Cp, serum Cu, serum SOD, and HbA1c levels by using commercially available kits. The SPSS, version 21, was used for data analysis. Results: The reduced FVC (p-value <0.001), FEV1 (p-value <0.001), and PEFR (p-value <0.001) were found in both groups of diabetes. However, the lower levels of serum Cu (p-value <0.001), SOD (p-value <0.001), and significantly increased values of FEV1/ FVC (p-value <0.001) and Cp levels (p-value 0.030) were found only in T2D group as compared to T1D and controls. The study found no significant correlation of PFTs and serum Cp, Cu, and SOD levels in patients suffering from T1D and T2D. Conclusion: Hyperglycemia leads to more non-enzymatic glycosylation of tissue proteins that reflects reduced PFTs and increased Cp; particularly in T2D, which may alter lung tissue's physiology. Moreover, the study showed no correlation of PFTs with the Cp, Cu, and SOD in patients suffering from T1D and T2D.
