Genetic Evidence for PLASMINOGEN as a Shared Genetic Risk Factor of Coronary Artery Disease and Periodontitis. (February 2015)

• Record Type: Journal Article
• Authors: Schaefer, Arne S.; Bochenek, Gregor; Jochens, Arne; Ellinghaus, David; Dommisch, Henrik; Güzeldemir-Akçakanat, Esra; Graetz, Christian; Harks, Inga; Jockel-Schneider, Yvonne; Weinspach, Knut; Meyle, Joerg; Eickholz, Peter; Linden, Gerry J.; Cine, Naci; Nohutcu, Rahime; Weiss, Ervin; Houri-Haddad, Yael; Iraqi, Fuad; Folwaczny, Mathias; Noack, Barbara; Strauch, Konstantin; Gieger, Christian; Waldenberger, Melanie; Peters, Annette; Wijmenga, Cisca; Yilmaz, Engin; Lieb, Wolfgang; Rosenstiel, Philip; Doerfer, Christof; Bruckmann, Corinna; Erdmann, Jeannette; König, Inke; Jepsen, Søren; Loos, Bruno G.; Schreiber, Stefan;
• Is Part Of: Circulation. Volume 8:Number 1(2015)
• Publication Date: 2015-02
• Subjects: Arrhythmia -- Periodicals; Heart -- Electric properties -- Periodicals; 616.1042
• DOI: 10.1161/CIRCGENETICS.114.000554
• Languages: English
• ISSNs: 1942-325X

Abstract

<abstract> <title> <x xml:space="preserve">Abstract</x> </title> <sec> <title>Background—</title> <p>Genetic studies demonstrated the presence of risk alleles in the genes <italic>ANRIL</italic> and <italic>CAMTA1/VAMP3</italic> that are shared between coronary artery disease (CAD) and periodontitis. We aimed to identify further shared genetic risk factors to better understand conjoint disease mechanisms.</p> </sec> <sec> <title>Methods and Results—</title> <p>In-depth genotyping of 46 published CAD risk loci of genome-wide significance in the worldwide largest case–control sample of the severe early-onset phenotype aggressive periodontitis (AgP) with the Illumina Immunochip (600 German AgP cases, 1448 controls) and the Affymetrix 500K array set (283 German AgP cases and 972 controls) highlighted <italic>ANRIL</italic> as the major risk gene and revealed further associations with AgP for the gene <italic>PLASMINOGEN</italic> (<italic>PLG</italic>; rs4252120: <italic>P</italic>=5.9×10<sup>−5</sup>; odds ratio, 1.27; 95% confidence interval, 1.3–1.4 [adjusted for smoking and sex]; 818 cases; 5309 controls). Subsequent combined analyses of several genome-wide data sets of CAD and AgP suggested <italic>TGFBRAP1</italic> to be associated with AgP (rs2679895: <italic>P</italic>=0.0016; odds ratio, 1.27 [95% confidence interval, 1.1–1.5]; 703 cases; 2.143 controls) and CAD (<italic>P</italic>=0.0003; odds ratio, 0.84 [95% confidence interval, 0.8–0.9]; n=4117 cases; 5824 controls). The study further provides evidence that in addition to <italic>PLG</italic>, the currently known shared susceptibility loci of CAD and periodontitis, <italic>ANRIL</italic> and <italic>CAMTA1/VAMP3</italic>, are subjected to transforming growth factor-β regulation.</p> </sec> <sec> <title>Conclusions—</title> <p> <italic>PLG</italic> is the third replicated shared genetic risk factor of atherosclerosis and periodontitis. All known shared risk genes of CAD and periodontitis are members of transforming growth factor-β signaling.</p> </sec> </abstract>