TRPM2, PDLIM5, BCL3, CD14, GBA Genes as Feasible Markers for Premature Coronary Heart Disease Risk

Area of Science:

• Genetics and Molecular Biology
• Cardiovascular Disease Research
• Biomarker Discovery

Background:

• Familial hypercholesterolemia (FH) is a genetic disorder causing severely elevated LDL cholesterol, a major risk factor for premature coronary heart disease (CHD).
• Identifying genetic markers for familial coronary heart disease (FH-CHD) in FH patients is crucial for early detection and intervention.

Purpose of the Study:

• To identify and validate genes associated with the development of familial coronary heart disease (FH-CHD) in individuals with familial hypercholesterolemia (FH).
• To explore potential gene expression profiles that differentiate FH and FH-CHD from healthy controls and other hypercholesterolemia groups.

Main Methods:

• Whole blood transcriptome analysis using next-generation sequencing in a cohort of 30 Thai male volunteers (controls, hypercholesterolemia, FH, CHD, FH-CHD).
• Selection and functional analysis of differentially expressed genes common to FH and FH-CHD groups.
• Quantitative real-time PCR (qRT-PCR) validation of selected candidate genes (TRPM2, PDLIM5, BCL3, GBA) in all participants.

Main Results:

• Fifty-five intersecting genes were found to be differentially expressed between FH and FH-CHD groups.
• Ten candidate genes, including TRPM2, PDLIM5, BCL3, and GBA, were selected for validation based on their potential roles in inflammation and CHD pathogenesis.
• TRPM2, PDLIM5, and BCL3 mRNA expression were significantly upregulated, while GBA was significantly downregulated in both FH and FH-CHD groups compared to controls.

Conclusions:

• The genes TRPM2, PDLIM5, BCL3, and GBA show significant differential expression patterns in individuals with FH and FH-CHD.
• These genes represent promising preliminary candidates for the development of novel predictive biomarkers for familial coronary heart disease (FH-CHD).