High prevalence of a mutation in the factor V gene within the U.K. population: relationship to activated protein C resistance and familial thrombosis

Abstract

Recent findings have indicated the importance of factor V (FV) in causing resistance to activated protein C (APC) in a high proportion of patients with venous thrombosis. This prompted us to investigate whether resistance could be due to defective inactivation of FVa by APC. Consequently, we amplified a 3.2 kb fragment of the FV gene sequence encoding the heavy chain APC cleavage site. DNA analysis showed a guanine to adenine transition at nucleotide 1691 in all affected members of two families with inherited APC resistance associated with thrombosis and confirmed suspected homozygosity in two individuals. The mutation, in heterozygous form, was also found in approximately 3.5% of our normal population (n = 144) and correlated with low APC resistance. The high prevalence of this mutation suggests that it may be a major contributory factor in early thrombosis.

Hereditary resistance to activated protein C: An uncommon risk factor for thromboembolic disease in lupus patients with antiphospholipid antibodies

“…Abnormal liver function findings have been described in 20-49% of allograft recipients receiving cyclosporin A (CSA) (1,2). This was usually of little significance; however, clinically important hepatotoxicity occurred in -4% of patients (2).…”

“…Considering its pathologic significance, the prevalence of the factor V Leiden gene is relatively high (3-11%) in unselected white populations (1)(2)(3). Factor V Leiden is virtually absent in Asian and black-African populations, and appears to have an intermediate prevalence in AfricanAmericans (2,4,5).…”

“…Factor V genotypes were determined by polymerase chain reaction (PCR) amplification of DNA from white blood cells. Primers straddled a 143-basepair segment of the factor V gene, which includes codon 506 (1). PCR products digested with Mnl I yielded fragments of 25, 37, and 81 bp when they were from the normal factor V allele, and 2.5 and 118 bp when derived from factor V Leiden.…”

A common polymorphism in the tumour necrosis factor‐alpha gene associated with high TNF levels is not a risk factor for venous thromboembolism

“…Factor V (nt1691) genotyping (factor V Leiden) was performed as previously described (Beauchamp et al, 1994). Statistics.…”

Activated protein C resistance, data from a population-based case…control study

“…In-house method (n-APC-SR) APC resistance, in the majority of cases due to factor V Leiden mutation, has been reported äs being common in the general Population, with a prevalence of 3-7% of subjects in different countries (Koster et al, 1993;Beauchamp et al, 1994;Berüna et al, 1994;. This alteration -to date mainly diagnosed by clotting methods only -has been quoted äs the single most frequent abnormality in patients suffering from thrombotic episodes (Faioni et cd, 1993;Griffin etal, 1993;Koster et al, 1993;Cadroyetfl/, 1994;Cushmanei al, 1994;Halbmayer et al, 1994;Legnani et al, 1994;.…”