title: Genetic evidence for PLASMINOGEN as a shared genetic risk factor of coronary artery disease and periodontitis.
abstract: 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.
  
  
  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.forename: Arne S
authors.initials: AS
authors.lastname: Schaefer
authors.forename: Gregor
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authors.lastname: Bochenek
authors.forename: Arne
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authors.lastname: Jochens
authors.forename: David
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authors.lastname: Ellinghaus
authors.forename: Henrik
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authors.lastname: Dommisch
authors.forename: Esra
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authors.lastname: Güzeldemir-Akçakanat
authors.forename: Christian
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authors.lastname: Graetz
authors.forename: Inga
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authors.lastname: Harks
authors.forename: Yvonne
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authors.lastname: Jockel-Schneider
authors.forename: Knut
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authors.lastname: Weinspach
authors.forename: Joerg
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authors.lastname: Meyle
authors.forename: Peter
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authors.lastname: Eickholz
authors.forename: Gerry J
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authors.lastname: Linden
authors.forename: Naci
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authors.lastname: Cine
authors.forename: Rahime
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authors.lastname: Nohutcu
authors.forename: Ervin
authors.initials: E
authors.lastname: Weiss
authors.forename: Yael
authors.initials: Y
authors.lastname: Houri-Haddad
authors.forename: Fuad
authors.initials: F
authors.lastname: Iraqi
authors.forename: Mathias
authors.initials: M
authors.lastname: Folwaczny
authors.forename: Barbara
authors.initials: B
authors.lastname: Noack
authors.forename: Konstantin
authors.initials: K
authors.lastname: Strauch
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.forename: Annette
authors.initials: A
authors.lastname: Peters
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Engin
authors.initials: E
authors.lastname: Yilmaz
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Lieb
authors.forename: Philip
authors.initials: P
authors.lastname: Rosenstiel
authors.forename: Christof
authors.initials: C
authors.lastname: Doerfer
authors.forename: Corinna
authors.initials: C
authors.lastname: Bruckmann
authors.forename: Jeannette
authors.initials: J
authors.lastname: Erdmann
authors.forename: Inke
authors.initials: I
authors.lastname: König
authors.forename: Søren
authors.initials: S
authors.lastname: Jepsen
authors.forename: Bruno G
authors.initials: BG
authors.lastname: Loos
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics; D003324:Coronary Artery Disease / Q000235:genetics*; D005260:Female; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D010518:Periodontitis / Q000235:genetics*; D010958:Plasminogen; D062085:RNA, Long Noncoding / Q000235:genetics; D012307:Risk Factors; D015534:Trans-Activators / Q000235:genetics; D051040:Vesicle-Associated Membrane Protein 3 / Q000235:genetics
chemical_list: C487554:CAMTA1 protein, human; C561518:CDKN2B antisense RNA, human; D002135:Calcium-Binding Proteins; D062085:RNA, Long Noncoding; D015534:Trans-Activators; C494946:VAMP3 protein, human; D051040:Vesicle-Associated Membrane Protein 3; D010958:Plasminogen
keywords: coronary artery disease; genetic association studies; periodontitis; plasminogen