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.
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.
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