Risk of Stroke in Young Women and Two Prothrombotic Mutations: Factor V Leiden and Prothrombin Gene Variant (G20210A)

Abstract

Background and Purpose-Factor V Leiden and a prothrombin gene variant, G20210A, are mutations associated with a thrombotic risk. The aim of our study was to assess whether these mutations increase the risk of stroke in women under 45 years of age. Methods-We conducted a case-control study in western Washington state. Case patients were women aged 18 to 44 years with a first stroke (nϭ106). Control subjects were women without stroke recruited from the same region by use of random-digit telephone dialing (nϭ391). All were interviewed and provided blood specimens, which were genotyped for these mutations. Results-Factor V Leiden was found in 0.9% of case patients, a single patient with a subarachnoid hemorrhage, and in 4.1% of control subjects. The odds ratio (OR) for any stroke was 0.2 (95% confidence interval [CI], 0.03 to 1.7). The prothrombin variant was found in 1.9% of case patients, 1 with a venous stroke and 1 with an ischemic stroke, and in 1.6% of control subjects. The OR for any stroke was 1.48 (95% CI, 0.14 to 9.17). ORs for stroke types were also not statistically significant. Conclusions-In this study, neither factor V Leiden nor the prothrombin variant (G20210A) was an important risk factor for stroke in young women. In this setting, screening for these mutations cannot be recommended. Unanswered by this study is whether screening would be useful in select patients, such as those with a strong family history of thrombophilia or those with venous strokes. (Stroke. 1998;29:577-580.)Key Words: cerebrovascular disorders Ⅲ mutation Ⅲ factor V Ⅲ prothrombin F actor V Leiden and a recently described variant of the prothrombin gene are both clotting factor mutations that are associated with an increased tendency for venous thrombosis.1-4 Factor V Leiden is a single-point mutation on the factor V gene in which adenine is substituted for guanine at nucleotide position 1691. The mutation results in a change in the factor V molecule where activated protein C would normally cleave and partially inactivate factor V. The result is a resistance to activated protein C.1,2 In a recently described prothrombin variant, adenine is substituted for guanine at position 20210 (G20210A) in the noncoding 3Ј terminal end of the prothrombin gene. 3,4 This variant is associated with increased prothrombin levels. Although the prothrombin molecule is normal, its expression is not. Factor V Leiden is a relatively common hereditary abnormality with a 3% to 5% prevalence of heterozygous carriers, 2 whereas the prothrombin variant, at 1% to 3%, is less prevalent.3,4 Although the association of these mutations with venous thrombosis has been demonstrated, 1-4 the association with arterial disease has not. As recently reviewed, the studies have not been consistent with respect to an association of factor V Leiden with coronary artery disease and myocardial infarction, 5 and the studies of the prothrombin variant are limited. 6 Although information on the prothrombin variant in patients with ischemic stroke is limited to a single negative...

Prevalence Of Thrombophilic Mutations In Ischemic Stroke Patients In Isparta, Turkey

“…Several studies have reported that FVL mutation is not an important risk factor for ischemic stroke (32)(33)(34)(35)(36). In contrast, the present study demonstrated a higher frequency of homozygous and heterozygous FVL mutations in stroke patients than in controls.…”

“…In contrast, the present study demonstrated a higher frequency of homozygous and heterozygous FVL mutations in stroke patients than in controls. The frequency of this mutation in stroke patients was higher than that reported in previous studies (33)(34)(35)(36)(37)(38)(39). Notably, the frequency of the FVL mutation in healthy individuals was similar to that of the general society.…”

“…The role of the prothrombin G20210A mutation in ischemic stroke is controversial (34,40,41,48,(50)(51)(52)(53). The present study shows that the prothrombin G20210A mutation is not associated with stroke and is not important in the case of ischemic stroke.…”

Determination of Prothrombotic Gene Polymorphisms and Stroke Risk Factors in Young Ischemic Stroke Patients

“…FVL mutasyonu, Faktör V geninin 1691'inci nükleotidinde arginin yerine glutamin gelmesi ile oluşan bir nokta mutasyonudur. Türklerde FVL mutasyonu %7,1-10,4 olarak en sık mutasyonlardan birisidir 8 . FVL mutasyonu heterezigot hastalarda tromboz riski sağlıklı bireylere göre 7, homozigotlarda ise 80 kat daha fazla tespit edilmiştir 9 .…”

“…Bir çalışmada Protrombin G20210A mutasyonu heterozigot taşıyıcılığı serebral ven trombozlu hastaların %20'sinde bildirilmiştir. Aynı zamanda, Protrombin G20210A mutasyonu arteriyel tromboz riskini de arttırmaktadır 8 .…”