BACKGROUND: Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 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. METHODS AND RESULTS: 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 ANRIL as the major risk gene and revealed further associations with AgP for the gene PLASMINOGEN (PLG; rs4252120: P=5.9×10(-5); 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 TGFBRAP1 to be associated with AgP (rs2679895: P=0.0016; odds ratio, 1.27 [95% confidence interval, 1.1-1.5]; 703 cases; 2.143 controls) and CAD (P=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 PLG, the currently known shared susceptibility loci of CAD and periodontitis, ANRIL and CAMTA1/VAMP3, are subjected to transforming growth factor-β regulation. CONCLUSIONS: PLG 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.
BACKGROUND: Genetic studies demonstrated the presence of risk alleles in the genes ANRIL and CAMTA1/VAMP3 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. METHODS AND RESULTS: 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 ANRIL as the major risk gene and revealed further associations with AgP for the gene PLASMINOGEN (PLG; rs4252120: P=5.9×10(-5); 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 TGFBRAP1 to be associated with AgP (rs2679895: P=0.0016; odds ratio, 1.27 [95% confidence interval, 1.1-1.5]; 703 cases; 2.143 controls) and CAD (P=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 PLG, the currently known shared susceptibility loci of CAD and periodontitis, ANRIL and CAMTA1/VAMP3, are subjected to transforming growth factor-β regulation. CONCLUSIONS: PLG 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.
Authors: Matthias Munz; Gesa M Richter; Bruno G Loos; Søren Jepsen; Kimon Divaris; Steven Offenbacher; Alexander Teumer; Birte Holtfreter; Thomas Kocher; Corinna Bruckmann; Yvonne Jockel-Schneider; Christian Graetz; Ilyas Ahmad; Ingmar Staufenbiel; Nathalie van der Velde; André G Uitterlinden; Lisette C P G M de Groot; Jürgen Wellmann; Klaus Berger; Bastian Krone; Per Hoffmann; Matthias Laudes; Wolfgang Lieb; Andre Franke; Jeanette Erdmann; Henrik Dommisch; Arne S Schaefer Journal: Eur J Hum Genet Date: 2018-09-14 Impact factor: 4.246
Authors: Y H Yu; L Doucette-Stamm; J Rogus; K Moss; R Y L Zee; B Steffensen; P M Ridker; J E Buring; S Offenbacher; K Kornman; D I Chasman Journal: J Dent Res Date: 2018-06-21 Impact factor: 6.116
Authors: A Shusterman; M Munz; G Richter; S Jepsen; W Lieb; B Krone; P Hoffman; M Laudes; J Wellmann; K Berger; T Kocher; S Offenbacher; K Divaris; A Franke; S Schreiber; H Dommisch; E Weiss; A S Schaefer; Y Houri-Haddad; F A Iraqi Journal: J Dent Res Date: 2017-05-03 Impact factor: 6.116
Authors: F David Carmona; Augusto Vaglio; Sarah L Mackie; José Hernández-Rodríguez; Paul A Monach; Santos Castañeda; Roser Solans; Inmaculada C Morado; Javier Narváez; Marc Ramentol-Sintas; Colin T Pease; Bhaskar Dasgupta; Richard Watts; Nader Khalidi; Carol A Langford; Steven Ytterberg; Luigi Boiardi; Lorenzo Beretta; Marcello Govoni; Giacomo Emmi; Francesco Bonatti; Marco A Cimmino; Torsten Witte; Thomas Neumann; Julia Holle; Verena Schönau; Laurent Sailler; Thomas Papo; Julien Haroche; Alfred Mahr; Luc Mouthon; Øyvind Molberg; Andreas P Diamantopoulos; Alexandre Voskuyl; Elisabeth Brouwer; Thomas Daikeler; Christoph T Berger; Eamonn S Molloy; Lorraine O'Neill; Daniel Blockmans; Benedicte A Lie; Paul Mclaren; Timothy J Vyse; Cisca Wijmenga; Yannick Allanore; Bobby P C Koeleman; Jennifer H Barrett; María C Cid; Carlo Salvarani; Peter A Merkel; Ann W Morgan; Miguel A González-Gay; Javier Martín Journal: Am J Hum Genet Date: 2016-12-29 Impact factor: 11.025