Genetic risk score of NOS gene variants associated with myocardial infarction correlates with coronary incidence across Europe

PLoS One. 2014 May 7;9(5):e96504. doi: 10.1371/journal.pone.0096504. eCollection 2014.

Abstract

Coronary artery disease (CAD) mortality and morbidity is present in the European continent in a four-fold gradient across populations, from the South (Spain and France) with the lowest CAD mortality, towards the North (Finland and UK). This observed gradient has not been fully explained by classical or single genetic risk factors, resulting in some cases in the so called Southern European or Mediterranean paradox. Here we approached population genetic risk estimates using genetic risk scores (GRS) constructed with single nucleotide polymorphisms (SNP) from nitric oxide synthases (NOS) genes. These SNPs appeared to be associated with myocardial infarction (MI) in 2165 cases and 2153 controls. The GRSs were computed in 34 general European populations. Although the contribution of these GRS was lower than 1% between cases and controls, the mean GRS per population was positively correlated with coronary incidence explaining 65-85% of the variation among populations (67% in women and 86% in men). This large contribution to CAD incidence variation among populations might be a result of colinearity with several other common genetic and environmental factors. These results are not consistent with the cardiovascular Mediterranean paradox for genetics and support a CAD genetic architecture mainly based on combinations of common genetic polymorphisms. Population genetic risk scores is a promising approach in public health interventions to develop lifestyle programs and prevent intermediate risk factors in certain subpopulations with specific genetic predisposition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Coronary Artery Disease / epidemiology*
  • Coronary Artery Disease / genetics
  • Europe / epidemiology
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Incidence
  • Male
  • Myocardial Infarction / genetics*
  • Nitric Oxide Synthase / genetics*
  • Polymorphism, Single Nucleotide*

Substances

  • Nitric Oxide Synthase

Grants and funding

This research has been supported by the Ministerio de Ciencia y Tecnología CGL2008-03955 and CGL2011-27866 projects to PM (http://www.idi.mineco.gob.es/); the Ministerio de Ciencia y Tecnología Predoctoral Grant (BES-2009-016334) and Travel Grant (EEBB-2011-44310) to RCT (http://www.idi.mineco.gob.es/); and the Beatriu de Pinós postdoctoral grant (2009 BP-B 00274) to MV (http://www10.gencat.cat/agaur_web/AppJava/index.jsp). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.