Unraveling the genetic basis of subclinical atherosclerosis: Early genetic detection can improve cardiovascular prevention.

IF 1.6 4区医学 Q3 CARDIAC & CARDIOVASCULAR SYSTEMS

Revista Portuguesa De Cardiologia Pub Date : 2025-03-06 DOI:10.1016/j.repc.2025.01.003

Débora Sá, Maria Isabel Mendonça, Marco Serrão, Francisco Sousa, Gonçalo Abreu, Eva Henriques, Sofia Borges, Sónia Freitas, Mariana Rodrigues, Graça Guerra, Ilídio Ornelas, António Drumond, Ana Célia Sousa, Roberto Palma Dos Reis

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引用次数: 0

Abstract

Introduction and objectives: Decoding the genetic basis of coronary artery disease (CAD) through an intermediate phenotype - coronary calcification - can help us to better understand this deadly disease and enable the creation of better therapeutic strategies. This work aims to assess the relationship between a set of single nucleotide polymorphisms (SNPs) previously associated with CAD and coronary artery calcium (CAC) score in a Portuguese asymptomatic population.

Methods: A prospective study was conducted in a cohort of 1284 subjects (aged 59.3±8.9 years, 73.6% males) without CAD. CAC score was performed using cardiac computed tomography. Thirty-three SNPs were genotyped using TaqMan real-time PCR. Anthropometric, conventional, and biochemical risk factors were evaluated. Bivariate and multivariate regression analysis estimated variables associated with the CAC score.

Results: PHACTR1 rs1332844 C>T, a downstream regulator of the endothelin-1 gene, showed a significant association with CAC score (p=0.015), together with CDKN2B-AS1 variants rs4977574 A>G (p=0.002) and rs1333049 G>C (p=0.010) in the 9p21.3 locus. MTHFD1L rs6922269 G>A variant encoding a mitochondrial enzyme responsible for homocysteine remethylating showed protection against artery calcification (p=0.013). After multivariate logistic regression, PHACTR1 rs1332844 (CT+TT) (OR=1.478; p=0.009) and CDKN2B-AS1 rs4977574 (GG) (OR=1.479; p=0.002) remained in the equation as independently associated with arterial calcification. MTHFD1L rs6922269 (AA) also remained associated with a lower CAC score (OR=0.558; p=0.027).

Conclusion: This study showed that three genetic variants previously linked with CAD are associated with CAC in asymptomatic populations. Understanding these genetic factors, combined with conventional risk factors, could guide lifestyle changes or pharmacologic interventions to mitigate CAD risk before the disease becomes clinical.

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揭示亚临床动脉粥样硬化的遗传基础：早期基因检测可以改善心血管疾病的预防。

前言和目的：通过中间表型-冠状动脉钙化-解码冠状动脉疾病（CAD）的遗传基础，可以帮助我们更好地了解这种致命疾病，并使创造更好的治疗策略成为可能。本研究旨在评估葡萄牙无症状人群中与冠心病相关的一组单核苷酸多态性（snp）与冠状动脉钙（CAC）评分之间的关系。方法：前瞻性研究纳入1284例无CAD患者（年龄59.3±8.9岁，男性73.6%）。采用心脏计算机断层扫描进行CAC评分。采用TaqMan实时PCR对33个snp进行基因分型。评估人体测量、常规和生化危险因素。双变量和多变量回归分析估计了与CAC评分相关的变量。结果：内皮素-1基因下游调控因子PHACTR1 rs1332844 C>T与CAC评分显著相关（p=0.015），与CDKN2B-AS1变异rs4977574 a >G （p=0.002）和rs1333049 G>C （p=0.010）在9p21.3位点存在显著相关性。MTHFD1L rs6922269 G>编码负责同型半胱氨酸再甲基化的线粒体酶的变体显示出对动脉钙化的保护作用（p=0.013）。多因素logistic回归后，PHACTR1 rs1332844 (CT+TT) （OR=1.478;p=0.009）和CDKN2B-AS1 rs4977574 (GG) （OR=1.479;p=0.002）仍与动脉钙化独立相关。MTHFD1L rs6922269 （AA）也与较低的CAC评分相关（OR=0.558;p=0.027）。结论：本研究表明，先前与CAD相关的三种遗传变异与无症状人群的CAC相关。了解这些遗传因素，结合传统的危险因素，可以指导生活方式的改变或药物干预，在疾病进入临床之前降低冠心病的风险。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Revista Portuguesa De Cardiologia CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

2.70

自引率

22.20%

发文量

205

审稿时长

54 days

期刊介绍： The Portuguese Journal of Cardiology, the official journal of the Portuguese Society of Cardiology, was founded in 1982 with the aim of keeping Portuguese cardiologists informed through the publication of scientific articles on areas such as arrhythmology and electrophysiology, cardiovascular surgery, intensive care, coronary artery disease, cardiovascular imaging, hypertension, heart failure and cardiovascular prevention. The Journal is a monthly publication with high standards of quality in terms of scientific content and production. Since 1999 it has been published in English as well as Portuguese, which has widened its readership abroad. It is distributed to all members of the Portuguese Societies of Cardiology, Internal Medicine, Pneumology and Cardiothoracic Surgery, as well as to leading non-Portuguese cardiologists and to virtually all cardiology societies worldwide. It has been referred in Medline since 1987.