Challenges of Precision Medicine for Atherosclerotic Cardiovascular Disease Based on Human Genome Information

Abstract

The official journal of the Japan Atherosclerosis Society and the Asian Pacific Society of Atherosclerosis and Vascular Diseases Review Precision or personalized medicine is currently gaining a lot of attention. Clinical evidence for its effectiveness has been established based on randomized clinical trials accounting for classical risk factors, such as hypertension, diabetes, and serum lipids. However, besides such classical risk factors, the genetic background should be considered, at least for heritable traits, including atherosclerotic cardiovascular disease (ASCVD). Such classical risk factors are almost always incidents that have already occurred in which it may be too late to start treatment, instead of indicators of presymptomatic state. Human genome information is associated with most traits, including ASCVD. Two methods of implementing precision medicine for ASCVD using human genome information are currently being investigated: the use of rare genetic variations that have large effect sizes and polygenic risk scores that are composed of multiple common genetic variations. This review article emphasizes the importance of clinical as well as genetic diagnoses when implementing precision medicine. Precision medicine should be considered based on comprehensive genetic analyses, encompassing rare to common genetic variations. is strongly associated with premature ASCVD 4). A single loss-of-function genetic mutation in the LDL receptor gene is associated with ASCVD via elevation of LDL cholesterol because LDL cholesterol is one of the causal factors of ASCVD 5). However, there are a substantial number of people who are at extremely high risk for inherited ASCVD that is not associated with serum lipids. Causal links between biology and ASCVD development in such inherited risk factors exist. Aim The following review describes conditions beginning with FH in which precision medicine for ASCVD seems to be quite effective, to other conditions in which precision medicine for ASCVD is currently being rigorously examined.

Putative Pathogenic Variants of ABCG5 and ABCG8 of Sitosterolemia in Patients With Hyper-Low-Density Lipoprotein Cholesterolemia

“…Thus, various genetic variants with unclear pathogenicity are identified. 17 18 This study proposed a useful scheme and identified the putative pathogenic variants of sitosterolemia, which can be helpful in genetic diagnosis in not only in Japan but also other countries worldwide. Notably, the scheme is reproducible anywhere, paving the way for further related research.…”

Investigating genes associated with cardiovascular disease among heart failure patients for translational research and precision medicine

“…Various genomics studies have been conducted recently to discover underlying genetic aetiology in CVD patients, especially those suspected of HF disease 47,48 . Several CVD‐related genes have significant mutations and expression differences among CVD patients 49–51 . To study chronic diseases with complex biological processes, it is imperative to take an integrative approach that combines multi‐omics data to highlight the intricacies associated with molecular functions.…”

“…47,48 Several CVD-related genes have significant mutations and expression differences among CVD patients. [49][50][51] To study chronic diseases with complex biological processes, it is imperative to take an integrative approach that combines multi-omics data to highlight the intricacies associated with molecular functions. In this study, we performed a multi-faceted approach involving WGS integrated with differential gene expression for HF and other CVD study.…”

Genetic Variants Associated with Supernormal Coronary Arteries

“…Genetic factors substantially affect the development of atherosclerotic cardiovascular disease 1) . In the previous decade, numerous studies actively investigated genetic variants contributing to this risk, finding that many of them are related to traditional clinical factors, whereas others are linked to noncoding genetic regions and uncertain pathways [2][3][4][5] .…”