Exome Sequencing Identified Susceptible Genes for High Residual Risks in Early-Onset Coronary Atherosclerotic Disease

IF 2.4 3区医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS

Clinical Cardiology Pub Date : 2024-12-14 DOI:10.1002/clc.70066

Runda Wu, Ya Su, Jianquan Liao, Juan Shen, Yuanji Ma, Wei Gao, Zheng Dong, Yuxiang Dai, Kang Yao, Junbo Ge

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引用次数: 0

Abstract

Aims

Despite the tremendous improvement in therapeutic medication and intervention for coronary atherosclerotic disease (CAD), residual risks remain. Exome sequencing enables identification of rare variants and susceptibility genes for residual risks of early-onset coronary atherosclerotic disease (EOCAD) with well-controlled conventional risk factors.

Methods

We performed whole-exome sequencing of subjects who had no conventional risk factors, defined as higher body mass index, smoking, hypertension and dyslipidemia, screened from 1950 patients with EOCAD (age ≤ 45 years, at least 50% stenosis of coronary artery by angiography), and selected control subjects from 1006 elder (age ≥ 65 years) with < 30% coronary stenosis. Gene-based association analysis and clinical phenotypic comparison were conducted.

Results

Subjects without defined conventional risk factors accounted for 4.72% of young patients. Totally, 6 genes might be associated with residual risk of EOCAD, namely CABP1 (OR = 22.19, p = 0.02), HLA-E (OR = 22.19, p = 0.02), TOE1 (OR = 33.6, p = 0.002), HPSE2 (OR = 11.1, p = 0.04), CHST14 (OR = 22.19, p = 0.02) as well as KLHL8 (OR = 22.19, p = 0.02). Phenotypic analysis displayed the levels of low-density lipoprotein cholesterol in carriers of mutations from CABP1, HLA-E, TOE1, and HPSE2 were significantly elevated compared to noncarriers. Notably, extracellular matrix-associated CHST14 and fibrinogen-associated KLHL8 both displayed possible correlation with increased neutrophil proportion and decreased monocyte percentage (both p < 0.05), exerting potential effects on the residual inflammatory risks of EOCAD.

Conclusion

The study identified six genes related to dyslipidemia and inflammation pathways with potential association with residual risk of EOCAD, which will contribute to precision-based prevention in these patients.

Trial Registration

The GRAND study was registered at www.clinicaltrials.gov on July 14, 2015, and the registry number is NCT 02496858.

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来源期刊

Clinical Cardiology 医学-心血管系统

CiteScore

5.10

自引率

3.70%

发文量

189

审稿时长

4-8 weeks

期刊介绍： Clinical Cardiology provides a fully Gold Open Access forum for the publication of original clinical research, as well as brief reviews of diagnostic and therapeutic issues in cardiovascular medicine and cardiovascular surgery. The journal includes Clinical Investigations, Reviews, free standing editorials and commentaries, and bonus online-only content. The journal also publishes supplements, Expert Panel Discussions, sponsored clinical Reviews, Trial Designs, and Quality and Outcomes.