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Background <p>Familial hypercholesterolemia (FH) is a significant risk factor for atherosclerosis due to elevated levels of low-density lipoprotein (LDL) cholesterol in arterial walls. This study aimed to determine the key genes involved in the development of atherosclerosis among FH patients.</p> Methods <p>The Affymetrix microarray dataset (GSE13985), which includes samples from five healthy controls and five FH patients, was obtained from the Gene Expression Omnibus (GEO) database. CEMiTool, an R package, was used to establish a modular gene co-expression network (mGCN) from 45,118 Affymetrix probe sets, followed by gene set enrichment analysis to determine the activity of modular gene regulation in the FH group, overrepresentation analysis to identify gene functions associated with FH, and hub gene detection.</p> Results <p>A scale-free topological network of gene co-expression modules (GCM) was built, and the activity of three important modules (M2, M4, and M5) was revealed to be upregulated in FH samples compared to healthy controls with putative involvement in atherosclerosis-related biological functions and pathways as follows: regulation of cell migration, cholesterol, inflammation, innate immunity, shear stress, and lipid pathways. Based on our integrated analyses, GCMs revealed seven hub genes, <i>RHOA</i>, <i>ACTB</i>, <i>LYN</i>, <i>ACTG1</i>, <i>BCL6</i>, <i>BCL2L1</i>, and <i>STAT3</i>, as promising biomarkers for developing and designing effective therapeutics for atherosclerosis in FH patients.</p> Conclusion <p>Seven hub genes have been identified as potential biomarkers for hypercholesterolemia, suggesting a role in the development of atherosclerosis in FH patients. These findings may aid in biomarker discovery and therapeutic targeting for FH-related atherosclerosis.</p>

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Gene co-expression module study identifies key genes and pathways underpinning hypercholesterolemia-induced atherosclerosis development

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月29日

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  • Muhammad-Redha Abdullah-Zawawi,
  • Muhammad Irfan Abdul Jalal,
  • Siti Aishah Sulaiman,
  • Nur Alyaa Afifah Md Shahri,
  • Rahman Jamal,
  • Nor Azian Abdul Murad

摘要

Background

Familial hypercholesterolemia (FH) is a significant risk factor for atherosclerosis due to elevated levels of low-density lipoprotein (LDL) cholesterol in arterial walls. This study aimed to determine the key genes involved in the development of atherosclerosis among FH patients.

Methods

The Affymetrix microarray dataset (GSE13985), which includes samples from five healthy controls and five FH patients, was obtained from the Gene Expression Omnibus (GEO) database. CEMiTool, an R package, was used to establish a modular gene co-expression network (mGCN) from 45,118 Affymetrix probe sets, followed by gene set enrichment analysis to determine the activity of modular gene regulation in the FH group, overrepresentation analysis to identify gene functions associated with FH, and hub gene detection.

Results

A scale-free topological network of gene co-expression modules (GCM) was built, and the activity of three important modules (M2, M4, and M5) was revealed to be upregulated in FH samples compared to healthy controls with putative involvement in atherosclerosis-related biological functions and pathways as follows: regulation of cell migration, cholesterol, inflammation, innate immunity, shear stress, and lipid pathways. Based on our integrated analyses, GCMs revealed seven hub genes, RHOA, ACTB, LYN, ACTG1, BCL6, BCL2L1, and STAT3, as promising biomarkers for developing and designing effective therapeutics for atherosclerosis in FH patients.

Conclusion

Seven hub genes have been identified as potential biomarkers for hypercholesterolemia, suggesting a role in the development of atherosclerosis in FH patients. These findings may aid in biomarker discovery and therapeutic targeting for FH-related atherosclerosis.