AIMS: Gain-of-function variants of genes encoding coagulation factor V (F5 G1691A) and prothrombin (F2 G20210A) cause hypercoagulability and are established risk factors for venous thrombosis. A meta-analysis of 66,155 cases and 91,307 controls found that either polymorphism is associated with a moderately increased risk of coronary artery disease (CAD). Because genetic factors play a particularly important role when acute myocardial infarction (AMI) occurs in the young, we chose to replicate these results by investigating, in the frame of a case-control study, a large cohort of Italian patients who had AMI before the age of 45years. METHODS AND RESULTS: In 1880 patients with AMI (1680 men and 210 women) and an equal number of controls, the minor A allele of F5 G1691A (2.6% frequency in cases and 1.7% in controls) was associated with an increased risk of AMI, the association remaining significant after adjustment for traditional risk factors (OR, 1.66; 95% CI, 1.15-2.38; P=0.006). The positive association with AMI for the minor A allele of F2 G20210A (2.5% frequency in cases and 1.9% in controls) did not reach statistical significance (OR, 1.32; 95% CI, 0.96-1.80; P=0.159). CONCLUSIONS: In a large cohort of young AMI patients the gain-of-function variant F5 G1691A was associated with an increased risk of AMI. The findings on the variant F2 G20210A confirmed the previously reported results, but the association was statistically not significant. These data suggest that a number of young patients with AMI carry gene variants associated with a procoagulant phenotype.
AIMS: Gain-of-function variants of genes encoding coagulation factor V (F5 G1691A) and prothrombin (F2 G20210A) cause hypercoagulability and are established risk factors for venous thrombosis. A meta-analysis of 66,155 cases and 91,307 controls found that either polymorphism is associated with a moderately increased risk of coronary artery disease (CAD). Because genetic factors play a particularly important role when acute myocardial infarction (AMI) occurs in the young, we chose to replicate these results by investigating, in the frame of a case-control study, a large cohort of Italian patients who had AMI before the age of 45years. METHODS AND RESULTS: In 1880 patients with AMI (1680 men and 210 women) and an equal number of controls, the minor A allele of F5 G1691A (2.6% frequency in cases and 1.7% in controls) was associated with an increased risk of AMI, the association remaining significant after adjustment for traditional risk factors (OR, 1.66; 95% CI, 1.15-2.38; P=0.006). The positive association with AMI for the minor A allele of F2 G20210A (2.5% frequency in cases and 1.9% in controls) did not reach statistical significance (OR, 1.32; 95% CI, 0.96-1.80; P=0.159). CONCLUSIONS: In a large cohort of young AMI patients the gain-of-function variant F5 G1691A was associated with an increased risk of AMI. The findings on the variant F2 G20210A confirmed the previously reported results, but the association was statistically not significant. These data suggest that a number of young patients with AMI carry gene variants associated with a procoagulant phenotype.
Authors: Kim Fechtel; Marika L Osterbur; Hildegard Kehrer-Sawatzki; Peter D Stenson; David N Cooper Journal: Hum Genet Date: 2011-05-03 Impact factor: 4.132
Authors: Gie Ken-Dror; Jackie A Cooper; Steve E Humphries; Fotios Drenos; Helen A Ireland Journal: Am J Epidemiol Date: 2011-09-12 Impact factor: 4.897
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