title: Association Between Coronary Artery Disease Genetic Variants and Subclinical Atherosclerosis: An Association Study and Meta-analysis.
abstract: OBJECTIVE
  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.
authors: Servicio de Cardiología, Hospital Universitario Josep Trueta, Girona, Spain; Grupo de Epidemiología y Genética Cardiovascular, IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Barcelona, Spain; Facultad de Medicina, Universidad de Girona, Girona, Spain.
authors: Michel
authors: M
authors: Zabalza
authors: Grupo de Epidemiología y Genética Cardiovascular, IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Barcelona, Spain; CIBER de Epidemiología y Salud Pública, Barcelona, Spain.
authors: Isaac
authors: I
authors: Subirana
authors: Grupo de Epidemiología y Genética Cardiovascular, IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Barcelona, Spain.
authors: Carla
authors: C
authors: Lluis-Ganella
authors: Grupo de Epidemiología y Genética Cardiovascular, IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Barcelona, Spain.
authors: Sergi
authors: S
authors: Sayols-Baixeras
authors: Academic Medical Center, Thoracic Surgery, Amsterdam, The Netherlands; Imagelab Online & Cardiovascular, Science Park, Matrix II, 1.08, Amsterdam, The Netherlands.
authors: Eric
authors: E
authors: de Groot
authors: ICICORELAB, Hospital Clínico Universitario, Valladolid, Spain.
authors: Roman
authors: R
authors: Arnold
authors: Laboratorio de Investigación Molecular, Hospital Universitario Miguel Servet, Instituto de Investigación Sanitaria de Aragón, Zaragoza, Spain.
authors: Ana
authors: A
authors: Cenarro
authors: 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; Facultad de Medicina, Universidad de Girona, Girona, Spain.
authors: Rafel
authors: R
authors: Ramos
authors: Grupo de Epidemiología y Genética Cardiovascular, IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Barcelona, Spain.
authors: Jaume
authors: J
authors: Marrugat
authors: Grupo de Epidemiología y Genética Cardiovascular, IMIM (Instituto Hospital del Mar de Investigaciones Médicas), Barcelona, Spain. Electronic address: relosua@imim.es.
authors: Roberto
authors: R
authors: Elosua
mesh_terms: D000483:Alleles; D050197:Atherosclerosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics; D018797:Cell Cycle Proteins; D054377:Chemokine CXCL12 / Q000235:genetics* / Q000378:metabolism; D003324:Coronary Artery Disease / Q000175:diagnosis / Q000209:etiology / Q000235:genetics; D003331:Coronary Vessels / Q000000981:diagnostic imaging*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D016601:RNA-Binding Proteins; D012307:Risk Factors
chemical_list: C515255:CXCL12 protein, human; D018797:Cell Cycle Proteins; D054377:Chemokine CXCL12; D009687:Nuclear Proteins; D016601:RNA-Binding Proteins; C517873:WDR12 protein, human
keywords: Ankle-brachial index; Aterosclerosis; Atherosclerosis; Carotid intima media thickness; Carotid stiffness; Genetic variants; Grosor intimomedial carotídeo; Meta-analysis; Metanálisis; Rigidez carotídea; Subclinical; Subclínica; Variantes genéticas; Índice tobillo-brazo