Gene expression profiling in elderly patients with familial hypercholesterolemia with and without coronary heart disease.

Background and Aims: Elderly familial hypercholesterolemia (FH) patients are at high risk of coronary heart disease (CHD) due to high cholesterol burden and late onset of effective cholesterol-lowering therapies. A subset of these individuals remains free from any CHD event, indicating the potential presence of protective factors. Identifying possible cardioprotective gene expression profiles could contribute to our understanding of CHD prevention and future preventive treatment. Therefore, this study aimed to investigate gene expression profiles in elderly event-free FH patients.
Methods: Expression of 773 genes was analysed using the Nanostring Metabolic Pathways Panel, in peripheral blood mononuclear cells (PBMCs) from FH patients ≥65 years without CHD (FH event-free, n = 44) and with CHD (FH CHD, n = 39), and from healthy controls ≥70 years (n = 39).
Results: None of the genes were differentially expressed between FH patients with and without CHD after adjusting for multiple testing. However, at nominal p < 0.05, we found 36 (5%) differentially expressed genes (DEGs) between the two FH groups, mainly related to lipid metabolism (e.g. higher expression of ABCA1 and ABCG1 in FH event-free) and immune responses (e.g. lower expression of STAT1 and STAT3 in FH event-free). When comparing FH patients to controls, the event-free group had fewer DEGs than the CHD group; 147 (19%) and 219 (28%) DEGs, respectively.
Conclusions: Elderly event-free FH patients displayed a different PBMC gene expression profile compared to FH patients with CHD. Differences in gene expression compared to healthy controls were more pronounced in the CHD group, indicating a less atherogenic gene expression profile in event-free individuals. Overall, identification of cardioprotective factors could lead to future therapeutic targets.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: MPB has received research grants and/or personal fees from Amgen and Sanofi, none of which are related to the content of this manuscript. JJC has received research grants and/or personal fees from Mills DA and Amgen, none of which are related to the content of this manuscript. AR has received personal fees from Rimfrost AS that are not related to the content of this manuscript. KR has received research grants and/or personal fees from Akcea, Amgen, Mills, Sanofi and Sunnovion, none of which are related to the content of this manuscript. KBH has received research grants and/or personal fees from Sanofi that are related to the content of this manuscript. The other authors have no financial relationships relevant to disclose.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)