Prevalence of factor V Leiden and prothrombin G20210A mutation in a large French population selected for nonthrombotic history: geographical and age distribution

Abstract

Among inherited risk factors for venous thrombosis, the most common are the FV-G1691A and FII-G20210A polymorphisms. The FV-G1691A polymorphism is preferentially observed in Europe, with differences between European countries. The FII-G20210A polymorphism is observed all over the world. The study was designed to compare the prevalence of the FV-G1691A and FII-G20210A polymorphisms in a large French population of unrelated individuals with no thrombotic disease history and to determine the age and geographical distributions. Over a period of 18 months, 6154 individuals were included throughout France and FV-G1691A and FII-G20210A polymorphisms were determined. The FV-G1691A prevalence was 3.84% (95% confidence interval 3.35-4.33) and the FII-G20210A prevalence was 3.07% (95% CI 2.63-3.51). A north-east/south-west gradient was observed in the FV-G1691A geographical distribution. No difference was observed in the geographical distribution of FII-G20210A polymorphism nor in the age distribution of the two polymorphisms. The prevalence of the two polymorphisms was similar whatever the blood group (O or non-O). Plasma D-dimers were significantly higher in healthy individuals with FV-G1691A but not in individuals with FII-G20210A. Thirty percent of variation in plasma prothrombin level was explained by environmental factors (serum cholesterol, age, oral contraception, hormonal replacement therapy, body mass index, sex) and genetic factors (FII-G20210A). As expected, individuals with FII-G20210A displayed higher plasma prothrombin level compared with individuals with wild type. However, this was not associated with a modification of the fibrin clot elastic modulus. This study shows a differential distribution of the two polymorphisms among the French territory. These polymorphisms confer a very mild hypercoagulable state as shown by the limited increased in basal D-dimers in mutated FV-G1691A populations and only a trend that does not reach statistical significance for FII-G20210A population.

Analysis of polymorphisms Leiden Factor V G1691A and prothrombin G20210A as risk factors for acute myocardial infarction

“…Here we report data strongly suggesting that at least the FII G20210A polymorphism might be considered a risk factor for acute myocardial infarction (AMI) in aged patients (55-80 years old). Actually, we observed a significant increase of 20210A FII allele associated to the reported higher plasma prothrombin level respect to the wild type ones (Mazoyer et al 2009). …”

“…A large debate exists on the risk association among Leiden Factor V (FV) G1691A and/or prothrombin (FII) G20210A polymorphisms and arterial disorders, despite of the several observations reported in a consistent collection of literature's papers showing data regarding different cohorts of patients affected by arterial thrombotic diseases, having different age ranges and geographical proveniences (Mazoyer et al 2009;Kahn 2003;Ridker et al 1995;Ozmen et al 2009;Ridker et al 1999;Kim and Becker 2003;Soare and Popa 2010).…”

“…Accordingly, no age stratification difference was observed in a study involving 6,154 French individuals. (Mazoyer et al 2009) .…”

Fibrin Clot Structure and Function

“…58 Individuals with the prothrombin G20210A allele showed normal fibrin elastic moduli. 59 Thrombin generation is a dynamic, localized process, and the formation of fibrin is determined by cellular procoagulant activity, which leads to spatial heterogeneity in clot structure associated with the distance of fibrin from the cell surface. 60 A denser fibrin network is formed within 10 m of the cell, as shown in experiments on human fibroblasts incubated with the prothrombinase complex and fibrinogen or plasma.…”

A meta-analysis of genome-wide association studies identifies ORM1 as a novel gene controlling thrombin generation potential

“…The MARTHA12 study is composed of an independent sample of 1245 VT patients that have been recruited between 2010 and 2012 according to the same criteria as the MARTHA patients. The FITENAT sample 35 consists of 543 French healthy individuals selected from health examination centers of the French Social Security. These subjects had no history of cardiovascular disease, diabetes, hypertension, renal nor hepatic failure and were not under anticoagulant therapy.…”