title: Inherited thrombophilic disorders in young adults with ischemic stroke and patent foramen ovale.
abstract: OBJECTIVE
  The pathogenic link between patent foramen ovale (PFO) and stroke remains unknown in most cases. We investigated the association between inherited thrombophilic disorders and PFO-related strokes in a series of young adults in the setting of a case-control study.
  
  
  METHODS
  We investigated 125 consecutive subjects (age, 34.7+/-7.3 years) with ischemic stroke and 149 age- and sex-matched control subjects. PFO was assessed in all patients with transcranial Doppler sonography with intravenous injection of agitated saline according to a standardized protocol. Genetic analyses for the factor V (FV)(G1691A) mutation, the prothrombin (PT)(G20210A) variant, and the TT677 genotype of methylenetetrahydrofolate reductase (MTHFR) were performed in all subjects.
  
  
  RESULTS
  A pathogenic role of PFO was presumed in 36 patients (PFO+). Interatrial right-to-left shunt either was not detected or was considered unrelated to stroke occurrence in the remaining 89 patients (PFO-). The PT(G20210A) variant was more frequent in the PFO+ group compared with control subjects and the PFO- group (PFO+ versus control subjects, 11% versus 2%; 95% CI, 0.04 to 0.94; PFO+ versus PFO-, 11% versus 1.1%; 95% CI, 1.09 to 109; P=0.047). A similar distribution was observed for subjects carrying either the PT(G20210A) variant or the FV(G1691A) mutation (PFO+ versus control subjects, 19.4% versus 5.3%; 95% CI, 0.08 to 0.75; PFO+ versus PFO-, 19.4% versus 3.3%; 95% CI, 1.45 to 26.1; P=0.021). Combined thrombophilic defects were observed in 3 subjects of the PFO+ group, in 2 control subjects (8.3% versus 1.3%; 95% CI, 0.01 to 0.66; P=0.015), and in 0 subjects in the PFO- group. A trend toward a difference in the frequency of the FV(G1691A) mutation between PFO+ and control subjects was found after bivariate analysis (11% versus 3.3%; P=0.068) but not after multinomial logistic regression analysis. No significant association was found in the distribution of the TT MTHFR genotype in the 3 groups.
  
  
  CONCLUSIONS
  In young adults, the PT(G20210A) variant and, to a lesser extent, the FV(G1691A) mutation may represent risk factors for PFO-related cerebral infarcts. A role of systemic thrombophilic disorders in the pathogenesis of this specific subtype of stroke may be hypothesized.
authors.affiliation: Clinica Neurologica, Università degli Studi di Brescia, Brescia, Italia. ale_pezzini@hotmail.com
authors.forename: Alessandro
authors.initials: A
authors.lastname: Pezzini
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Del Zotto
authors.forename: Mauro
authors.initials: M
authors.lastname: Magoni
authors.forename: Angelo
authors.initials: A
authors.lastname: Costa
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.forename: Nabil Maalikjy
authors.initials: NM
authors.lastname: Akkawi
authors.forename: Alberto
authors.initials: A
authors.lastname: Albertini
authors.forename: Deodato
authors.initials: D
authors.lastname: Assanelli
authors.forename: Luigi Amedeo
authors.initials: LA
authors.lastname: Vignolo
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000328:Adult; D002545:Brain Ischemia / Q000175:diagnosis / Q000235:genetics*; D016022:Case-Control Studies; D002544:Cerebral Infarction / Q000235:genetics; D005165:Factor V / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006344:Heart Septal Defects, Atrial / Q000150:complications* / Q000175:diagnosis; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000235:genetics; D011446:Prospective Studies; D011516:Prothrombin / Q000235:genetics; D020521:Stroke / Q000175:diagnosis / Q000235:genetics*; D013927:Thrombosis / Q000235:genetics
chemical_list: D005165:Factor V; D011516:Prothrombin; D000587:Oxidoreductases Acting on CH-NH Group Donors; D042965:Methylenetetrahydrofolate Reductase (NADPH2)