Identification of Differential Expressed Genes and Key Pathways in Monocytes and CD3+ T-Cells of Familial Hypercholesterolemia (FH) Patients

Abstract

Familial hypercholesterolemia (FH) is an autosomal dominant disorder, where molecular defects in PCSK9, APOE, and LDLR genes cause the elevation of serum LDL cholesterol levels. This condition results in an excess deposition of cholesterol in vascular tissues that hastens the process of atherosclerosis and elevates the risk of developing premature cardiovascular disease (CVD). The exact molecular mechanisms through which genetic defects contribute to alterations in lipid content and lipoprotein metabolism remain an under-researched area to date. Therefore, this study has sought to integrate the microarray gene expression data of two different cells (human circulating monocytes and CD3 positive T cells) (E-GEOD-6054 and E-GEOD-6088) of FH (with familial hypercholesterolemia, homozygous or heterozygous mutant for LDLR) in order to identify potential candidate genes and pathways associated with FH. We analyzed gene expression data in this study using the R software program using the Affy and Limma packages. In the human circulating monocytes expression dataset, a total of 957 and 618 genes were identified, which were expressed as LDLR heterozygous and homozygous, respectively, in FH patients, compared to the experimental controls. In the CD3+ T-cells, 431 and 410 genes were expressed as LDLR homozygous and heterozygous in FH patients compared to the experimental controls. In summary, by using integrated bioinformatics analysis, we were able to discern potential pathways and genes that play an important role in the development of FH, and could therefore be fruitful for future research efforts in this domain.