OBJECTIVE: The single nucleotide polymorphism (SNP) rs2995300 in the metalloproteinase-disintegrin gene ADAM8 has been shown to affect the areas of complicated coronary plaques and the risk of fatal myocardial infarction (MI) in men. This study was set up to further investigate the role of ADAM8 in MI. AIM: To investigate the possible association of the ADAM8 SNPs rs2995300 and rs2275725 with ADAM8 mRNA levels, serum soluble ADAM8 (sADAM8) concentrations, and MI risk. METHODS: Samples from the Finnish cardiovascular study (FINCAVAS, N=2156) and the angiography and genes study (ANGES, N=1000) were genotyped. Serum sADAM8 concentrations were determined with ELISA (N=443). ADAM8 mRNA levels in atherosclerotic plaques were analysed from the tampere vascular study (TVS, N=53) samples. RESULTS: A significantly increased MI risk for carriers of the rs2995300C allele and the rs2275725 A allele was revealed in the meta-analysis of the ANGES and FINCAVAS patient data (OR=1.42, P<0.001 and OR=1.43, P<0.001). The risk increase was comparable to that caused by smoking in these cohorts. The risk allele carriers also had higher sADAM8 serum concentrations. CONCLUSIONS: The risk alleles of the investigated ADAM8 SNPs were associated with elevated sADAM8 serum levels and MI risk. The present results implicate ADAM8 in the development of CVDs and suggest its prognostic and therapeutic potential.
OBJECTIVE: The single nucleotide polymorphism (SNP) rs2995300 in the metalloproteinase-disintegrin gene ADAM8 has been shown to affect the areas of complicated coronary plaques and the risk of fatal myocardial infarction (MI) in men. This study was set up to further investigate the role of ADAM8 in MI. AIM: To investigate the possible association of the ADAM8 SNPs rs2995300 and rs2275725 with ADAM8 mRNA levels, serum soluble ADAM8 (sADAM8) concentrations, and MI risk. METHODS: Samples from the Finnish cardiovascular study (FINCAVAS, N=2156) and the angiography and genes study (ANGES, N=1000) were genotyped. Serum sADAM8 concentrations were determined with ELISA (N=443). ADAM8 mRNA levels in atherosclerotic plaques were analysed from the tampere vascular study (TVS, N=53) samples. RESULTS: A significantly increased MI risk for carriers of the rs2995300C allele and the rs2275725 A allele was revealed in the meta-analysis of the ANGES and FINCAVAS patient data (OR=1.42, P<0.001 and OR=1.43, P<0.001). The risk increase was comparable to that caused by smoking in these cohorts. The risk allele carriers also had higher sADAM8 serum concentrations. CONCLUSIONS: The risk alleles of the investigated ADAM8 SNPs were associated with elevated sADAM8 serum levels and MI risk. The present results implicate ADAM8 in the development of CVDs and suggest its prognostic and therapeutic potential.
Authors: Tanja Pessi; Leena E Viiri; Emma Raitoharju; Nagora Astola; Ilkka Seppälä; Melanie Waldenberger; Kari Lounatmaa; Alun H Davies; Terho Lehtimäki; Pekka J Karhunen; Claudia Monaco Journal: Springerplus Date: 2015-04-30
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Authors: Lars Wallentin; Folkert W Asselbergs; Riyaz S Patel; Bakhtawar K Mahmoodi; Vinicius Tragante; Marcus E Kleber; Michael V Holmes; Amand F Schmidt; Raymond O McCubrey; Laurence J Howe; Kenan Direk; Hooman Allayee; Ekaterina V Baranova; Peter S Braund; Graciela E Delgado; Niclas Eriksson; Crystel M Gijsberts; Yan Gong; Jaana Hartiala; Mahyar Heydarpour; Gerard Pasterkamp; Salma Kotti; Pekka Kuukasjärvi; Petra A Lenzini; Daniel Levin; Leo-Pekka Lyytikäinen; Jochen D Muehlschlegel; Christopher P Nelson; Kjell Nikus; Anna P Pilbrow; W H Wilson Tang; Sander W van der Laan; Jessica van Setten; Ragnar O Vilmundarson; John Deanfield; Panos Deloukas; Frank Dudbridge; Stefan James; Ify R Mordi; Andrej Teren; Thomas O Bergmeijer; Simon C Body; Michiel Bots; Ralph Burkhardt; Rhonda M Cooper-DeHoff; Sharon Cresci; Nicolas Danchin; Robert N Doughty; Diederick E Grobbee; Emil Hagström; Stanley L Hazen; Claes Held; Imo E Hoefer; G Kees Hovingh; Julie A Johnson; Marcin P Kaczor; Mika Kähönen; Olaf H Klungel; Jari O Laurikka; Terho Lehtimäki; Anke H Maitland-van der Zee; Ruth McPherson; Colin N Palmer; Adriaan O Kraaijeveld; Carl J Pepine; Marek Sanak; Naveed Sattar; Markus Scholz; Tabassome Simon; John A Spertus; Alexandre F R Stewart; Wojciech Szczeklik; Joachim Thiery; Frank L J Visseren; Johannes Waltenberger; A Mark Richards; Chim C Lang; Vicky A Cameron; Axel Åkerblom; Guillaume Pare; Winfried März; Nilesh J Samani; Aroon D Hingorani; Jurriën M Ten Berg Journal: Circulation Date: 2020-07-13 Impact factor: 29.690