title: Do common prothrombotic mutations influence the risk of cerebral ischaemia in patients with patent foramen ovale? Systematic review and meta-analysis.
abstract: Conflicting results are available on the association of prothrombotic genetic abnormalities with patent foramen ovale (PFO)-related cerebral ischaemia. We comprehensively sought and identified studies of the association of both the factor V Leiden (FV(G1691A) mutation) and the prothrombin mutation (PT(G20210A) mutation) with PFO-related cerebral ischaemia and did meta-analyses to assess the evidence for such a relation. We analysed data from six eligible studies in 856 cases and 1,001 control subjects. Additional unpublished data from a new series including 463 subjects were also entered into the analysis. The PT(G20210A) variant was significantly associated with PFO-related stroke in comparison with both control subjects (odds ratio [OR] 3.85; 95% confidence interval [CI] 2.22 to 6.66) and non-PFO-associated stroke patients (OR 2.31; 95% CI 1.20 to 4.43), whereas a trend toward an association was observed for the FV(G1691A) mutation (OR 1.18; 95% CI 0.73 to 1.90, compared to control subjects; OR 1.14; 95% CI 0.62 to 2.09, compared to non-PFO-associated stroke patients). The status of carrier of either the FV(G1691A) mutation or the PT(G20210A) variant was associated with a risk for stroke of 1.98 (95% CI 1.38 to 2.83) and 1.62 (95% CI 1.03 to 2.57), as compared to control subjects and non-PFO-associated stroke patients, respectively. Addition of common prothrombotic genetic variants to standard initial screening may contribute to stratifying PFO-associated stroke patients at different risk of ischaemic events and targeting secondary prevention strategies.
authors.affiliation: Clinica Neurologica, Università degli Studi di Brescia P.le Spedali Civili, 1 25100 Brescia, Italia. ale_pezzini@hotmail.com
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pezzini
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.forename: Elisabetta Del
authors.initials: ED
authors.lastname: Zotto
authors.forename: Alessia
authors.initials: A
authors.lastname: Giossi
authors.forename: Irene
authors.initials: I
authors.lastname: Volonghi
authors.forename: Paolo
authors.initials: P
authors.lastname: Costa
authors.forename: Armin
authors.initials: A
authors.lastname: Grau
authors.forename: Mauro
authors.initials: M
authors.lastname: Magoni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Christoph
authors.initials: C
authors.lastname: Lichy
mesh_terms: D002545:Brain Ischemia / Q000097:blood / Q000235:genetics*; D005165:Factor V / Q000235:genetics*; D054092:Foramen Ovale, Patent / Q000097:blood / Q000150:complications / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D009154:Mutation; D016017:Odds Ratio; D011516:Prothrombin / Q000235:genetics*; D018570:Risk Assessment; D012307:Risk Factors; D020521:Stroke / Q000097:blood / Q000235:genetics*; D013927:Thrombosis / Q000097:blood / Q000235:genetics*
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin