The association of factor V Leiden with myocardial infarction is replicated in 1880 patients with premature disease.
OBJECTIVE
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.


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.
Mannucci
P M
PM
Centro Emofilia e Trombosi A. Bianchi Bonomi, Scientific Direction, IRCCS Fondazione Cà Granda Ospedale Maggiore, Università degli Studi di Milano, Milan, Italy. piermannuccio.mannucci@unimi.it
Asselta
R
R
Duga
S
S
Guella
I
I
Spreafico
M
M
Lotta
L
L
Merlini
P A
PA
Peyvandi
F
F
Kathiresan
S
S
Ardissino
D
D
D000328:Adult; D017668:Age of Onset; D000483:Alleles; D015331:Cohort Studies; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009203:Myocardial Infarction / Q000235:genetics*; D016017:Odds Ratio; D010641:Phenotype; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011516:Prothrombin / Q000235:genetics*; D012306:Risk
D017395:Plasminogen Activator Inhibitor 1; C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin