AUTHOR=Prasongsukarn Kriengchai , Dechkhajorn Wilanee , Benjathummarak Surachet , Maneerat Yaowapa 

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

JOURNAL=Frontiers in Genetics

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.598296

DOI=10.3389/fgene.2021.598296

ISSN=1664-8021

ABSTRACT=<p><bold>Background:</bold> Beyond non-genetic risk factors, familial hypercholesterolemia (FH) plays a major role in the development of CHD. FH is a genetic disorder characterized by heritable and severely elevated levels of low-density lipoprotein (LDL) cholesterol, which can lead to premature cardiovascular disease, particularly familial coronary heart disease (FH-CHD).</p><p><bold>Method:</bold> To explore genes indicating a risk of familial (premature) coronary heart disease (FH-CHD) development in FH, 30 Thai male volunteers were enrolled: 7 healthy controls (N), 6 patients with hypercholesterolemia (H), 4 with FH, 10 with CHD, and 3 with FH-CHD. Transcriptome data were investigated using next-generation sequencing analysis in whole blood (<italic>n</italic> = 3). Genes that were significantly expressed in both FH and FH-CHD, but not in N, H, and CHD groups, were selected and functionally analyzed.</p><p><bold>Results:</bold> The findings revealed that 55 intersecting genes were differentially expressed between FH and FH-CHD groups. Ten of the 55 genes (<italic>MAPK14</italic>, <italic>TRPM2</italic>, <italic>STARD8</italic>, <italic>PDLIM5</italic>, <italic>BCL3</italic>, <italic>BLOC1S5</italic>, <italic>GBA</italic>, <italic>RBMS1</italic>, <italic>CD14</italic>, and <italic>CD36</italic> were selected for validation. These 10 genes play potential roles in chronic inflammation and are involved in pathways related to pathogenesis of CHD. Using quantitative real-time PCR, we evaluated the mRNA expression of the selected genes in all 30 volunteers. <italic>TRPM2</italic>, <italic>PDLIM5</italic>, <italic>BCL3</italic> were significantly upregulated and <italic>GBA</italic> was significantly downregulated in both FH and FH-CHD compared with the N, H, and CHD groups.</p><p><bold>Conclusion:</bold> our preliminary investigation reveals that the <italic>TRPM2</italic>, <italic>PDLIM5</italic>, <italic>BCL3</italic>, and <italic>GBA</italic> genes may have potential for further development as predictive markers for FH-CHD.</p>