Evidence against heterozygous coagulation factor V 1691 G?A mutation with resistance to activated protein C being a risk factor for coronary artery disease and myocardial infarction

Abstract

The aim of our study was to determine the prevalence of the factor V mutation (position 1691 G-->A) in patients with angiographically diagnosed coronary artery disease and myocardial infarction and, as a control, in blood donors. This mutation has already been proved to be the main genetic risk factor for venous thrombosis. In order to detect this mutation in exon 10 of the factor V gene we established a microtiter plate based hybridization assay for the specific detection of wild-type and mutant sequences in factor V gene segments, obtained after amplification by polymerase chain reaction. This test enables us to screen a large number of samples. The mutation was detected in 29 of 317 coronary artery disease (CAD) patients (9.1%) and 18 of 190 blood donors (9.5%) investigated. The mean activated protein C resistance ratios were 3.18 and 3.11, with nearly identical distribution. No increased prevalence of the factor V mutation was found in the CAD group. In 10 of 29 CAD patients (35%) with the factor V 1691 G-->A mutation and in 124 of 288 CAD patients without the mutation (43%) there was a history of myocardial infarction. From our data we conclude that there is no increased risk of developing coronary atheroma or consecutive myocardial infarction resulting from the factor V mutation with protein C resistance.

Heterogeneous ethnic distribution of the factor v leiden mutation

“…Our data agree with these observations since this lower incidence may partly reflect the absence of the most important known cause of venous thrombophilia (the FVL mutation) in this ethnic group. The possibility that FVL might be a genetic risk factor for arterial thrombotic disease has been investigated in several studies, but with conflicting results (Prohaska et al, 1995;Kontula et al, 1995;van der Bom et al, 1996;Foley et al, 1997). However, a recent study demonstrated a clear relationship between the presence of FVL and increased predisposition for myocardial infarction in young women (Rosendaal et al, 1997).…”

Genetic Variation in Coagulation and Fibrinolytic Proteins and Their Relation With Acute Myocardial Infarction

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] From those, 12 studies were excluded because no solid diagnostic criteria for myocardial infarction were used, [17][18][19][20] there was inadequate delineation of cases, 21,22 or there was an inadequate spectrum of cases, [11][12][13][14][15][16] leaving a total of 6 studies in the analysis.…”

Factor V Leiden: The Copenhagen City Heart Study and 2 meta-analyses

“…Most studies on FVL and arterial thrombosis have demonstrated insignificant or borderline significant associations, some studies favoring a risk reduction in FVL carriers, [5][6][7][8][9][10][11][12][13][14][15][16] others an increase. The present study (1) estimated risk of thrombosis in atherosclerotic arteries (MI or IS) as well as risk of atherosclerosis without thrombosis (non-MI-ischemic heart disease [non-MI-IHD]) in FVL carriers, using a population-based study; (2) examined if FVL interacts with established cardiovascular risk factors in predicting MI, IS, and non-MI-IHD; and finally (3) systematically combined our data with previously published studies on FVL and risk of arterial thrombosis using meta-analyses.…”