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Review
. 2020 Nov 10;9(2):370-380.
doi: 10.1016/j.gendis.2020.11.003. eCollection 2022 Mar.

Pathogenesis of premature coronary artery disease: Focus on risk factors and genetic variants

Haiming Wang  1 , Zifan Liu  1 , Junjie Shao  2 , Min Jiang  1 , Xuechun Lu  3 , Lejian Lin  1 , Lin Wang  1 , Qiang Xu  1 , Haomin Zhang  3 , Xin Li  4 , Jingjing Zhou  1 , Yundai Chen  1 , Ran Zhang  1
Affiliations
Review

Pathogenesis of premature coronary artery disease: Focus on risk factors and genetic variants

Haiming Wang et al. Genes Dis. .

Abstract

The development of premature coronary artery disease (PCAD) is dependent on both genetic predisposition and traditional risk factors. Strategies for unraveling the genetic basis of PCAD have evolved with the advent of modern technologies. Genome-wide association studies (GWASs) have identified a considerable number of common genetic variants that are associated with PCAD. Most of these genetic variants are attributable to lipid and blood pressure-related single-nucleotide polymorphisms (SNPs). The genetic variants that predispose individuals to developing PCAD may depend on race and ethnicity. Some characteristic genetic variants have been identified in Chinese populations. Although translating this genetic knowledge into clinical applications is still challenging, these genetic variants can be used for CAD phenotype identification, genetic prediction and therapy. In this article we will provide a comprehensive review of genetic variants detected by GWASs that are predicted to contribute to the development of PCAD. We will highlight recent findings regarding CAD-related genetic variants in Chinese populations and discuss the potential clinical utility of genetic variants for preventing and managing PCAD.

Keywords: Genetic clinical applications; Genetic variants; Genome-wide association studies; Premature coronary artery disease; Single-nucleotide polymorphisms.

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Figures

Figure 1
Figure 1
The pathogenesis of premature coronary artery disease (PCAD) involves both traditional and genetic cardiovascular risk factors. The development of PCAD is dependent on both genetic predisposition and traditional risk factors. Traditional risk factors such as diabetes, hypertension, smoking, obesity, a high-energy diet, hypercholesterolemia, and a family history of coronary artery disease are associated with a high incidence of PCAD. Genetic variants in genes such as PCSK9, LDL-R, and NPC1L1 contribute to PCAD either directly or via traditional cardiovascular risk factors.
Figure 2
Figure 2
Single-nucleotide polymorphisms in the interleukin (IL)-1β/IL-6 signaling pathway contribute to atherosclerotic premature coronary artery disease (PCAD). The IL1-CCC, IL-6-147 g/c, and IL-17A polymorphisms are correlated with atherosclerosis and PCAD via their effects on the IL-1β/IL-6/C-reactive protein (CRP) inflammation pathway. Activation of the NLRP3 inflammasome results in the production of IL-1β and consequent downstream effects on IL-6 and CRP synthesis in the liver. IL-17 produced by activated T cells promotes the production of IL-6, which amplifies local inflammation.
Figure 3
Figure 3
Clinical outcomes and promising applications of genetic variants in premature coronary artery disease (PCAD). Genome-wide association studies have successfully identified genetic variants (in genes related to regulation of hypertension, LDL levels, and triglyceride levels) associated with the development of PCAD. Although translating this knowledge into clinical practice is still challenging, using this information to identify CAD phenotypes, predict the genetic risk of developing CAD, and develop genetic therapies for CAD based on inherited genetic variants is nevertheless a promising approach.
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