Variants of PCSK9 Gene Are Associated with Subclinical Atherosclerosis and Cardiometabolic Parameters in Mexicans. The GEA Project.

Erasmo Zamarrón-Licona,José Manuel Rodríguez-Pérez,Gilberto Vargas-Alarcón,Rosalinda Posadas-Sánchez,Manuel Alfonso Baños-González,Verónica Marusa Borgonio-Cuadra,Nonanzit Pérez-Hernández

doi:10.3390/diagnostics11050774

Abstract

Background: Coronary artery disease (CAD) is a chronic, inflammatory, and complex disease associated with vascular risk factors. Nowadays, the coronary artery calcium (CAC) is a specific marker of the presence and extent of atherosclerosis. Additionally, CAC is a predictor of future coronary events in asymptomatic individuals diagnosed with subclinical atherosclerosis (CAC > 0). In this study, our aim is to evaluate the participation of two polymorphisms of the PCSK9 gene as genetic markers for developing subclinical atherosclerosis and cardiometabolic risk factors in asymptomatic individuals. Methods: We analyzed two PCSK9 polymorphisms (rs2479409 and rs615563) in 394 individuals with subclinical atherosclerosis and 1102 healthy controls using real time- polymerase chain reaction (PCR). Results: Under various inheritance models adjusted for different confounding factors, the rs2479409 polymorphism was associated with an increased risk of developing subclinical atherosclerosis (OR = 1.53, P recessive = 0.041). Both polymorphisms were significantly associated with several cardiometabolic parameters. Conclusions: Our data suggest that rs2479409 polymorphism could be envisaged as a risk marker for subclinical atherosclerosis.

Highlights

Coronary artery disease (CAD) is a chronic, inflammatory, and complex disease, and it is considered the main cause of death worldwide
The proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key molecule which is synthesized and secreted mainly by hepatocytes, but with lower expression in the brain, kidney and intestine. This molecule has an important role in low-density lipoprotein cholesterol (LDL-C)
265 ancestry informative markers, and the results showed that all individuals in our sample had a similar genetic background; there was no genetic bias in the present study [23]

Summary

Introduction

Coronary artery disease (CAD) is a chronic, inflammatory, and complex disease, and it is considered the main cause of death worldwide. Epigenetic and genetic factors are considered to influence the development of CAD [2,4,5,6] In this sense, genetic research of human diseases has helped to identify gene variants with functional implications over several biological signaling pathways related to the vascular health process. Genetic research of human diseases has helped to identify gene variants with functional implications over several biological signaling pathways related to the vascular health process Among these pathways, the proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key molecule which is synthesized and secreted mainly by hepatocytes, but with lower expression in the brain, kidney and intestine. Our aim is to evaluate the participation of two polymorphisms of the PCSK9 gene as genetic markers for developing subclinical atherosclerosis and cardiometabolic risk factors in asymptomatic individuals. Conclusions: Our data suggest that rs2479409 polymorphism could be envisaged as a risk marker for subclinical atherosclerosis

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