Revista Española de Cardiología (English Edition) Revista Española de Cardiología (English Edition)
Rev Esp Cardiol. 2015;68:869-77 - Vol. 68 Num.10 DOI: 10.1016/j.rec.2014.10.023

Association Between Coronary Artery Disease Genetic Variants and Subclinical Atherosclerosis: An Association Study and Meta-analysis

Michel Zabalza a,b,c, Isaac Subirana b,d, Carla Lluis-Ganella b, Sergi Sayols-Baixeras b, Eric de Groot e,f, Roman Arnold g, Ana Cenarro h, Rafel Ramos c,i, Jaume Marrugat b, Roberto Elosua b,

a Servicio de Cardiología, Hospital Universitario Josep Trueta, Girona, Spain
b Grupo de Epidemiología y Genética Cardiovascular, IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Barcelona, Spain
c Facultad de Medicina, Universidad de Girona, Girona, Spain
d CIBER de Epidemiología y Salud Pública, Barcelona, Spain
e Academic Medical Center, Thoracic Surgery, Amsterdam, The Netherlands
f Imagelab Online & Cardiovascular, Science Park, Matrix II, 1.08, Amsterdam, The Netherlands
g ICICORELAB, Hospital Clínico Universitario, Valladolid, Spain
h Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain
i Unidad de Investigación en Atención Primaria, Institut d’Investigació en Atenció Primària (IDIAP) Jordi Gol, y Unidad Docente de Medicina de Familia de Girona, Institut Català de la Salut (ICS), Girona, Spain

Keywords

Genetic variants. Atherosclerosis. Carotid intima media thickness. Carotid stiffness. Ankle-brachial index. Meta-analysis. Subclinical.

Abstract

Introduction and objectives

Recent studies have identified several genetic variants associated with coronary artery disease. Some of these genetic variants are not associated with classical cardiovascular risk factors and the mechanism of such associations is unclear. The aim of the study was to determine whether these genetic variants are related to subclinical atherosclerosis measured by carotid intima media thickness, carotid stiffness, and ankle brachial index.

Methods

A cross-sectional study nested in the follow-up of the REGICOR cohort was undertaken. The study included 2667 individuals. Subclinical atherosclerosis measurements were performed with standardized methods. Nine genetic variants were genotyped to assess associations with subclinical atherosclerosis, individually and in a weighted genetic risk score. A systematic review and meta-analysis of previous studies that analyzed these associations was undertaken.

Results

Neither the selected genetic variants nor the genetic risk score were significantly associated with subclinical atherosclerosis. In the meta-analysis, the rs1746048 (CXCL12; n = 10581) risk allele was directly associated with carotid intima-media thickness (β = 0.008; 95% confidence interval, 0.001-0.015), whereas the rs6725887 (WDR12; n = 7801) risk allele was inversely associated with this thickness (β = −0.013; 95% confidence interval, –0.024 to –0.003).

Conclusions

The analyzed genetic variants seem to mediate their association with coronary artery disease through different mechanisms. Our results generate the hypothesis that the CXCL12 variant appears to influence coronary artery disease risk through arterial remodeling and thickening, whereas the WDR12 risk variant could be related to higher plaque vulnerability.

1885-5857/© 2015 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved

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