title: Cumulative effect of predisposing genotypes and their interaction with modifiable factors on the risk of ischemic stroke in young adults.
abstract: OBJECTIVE
  Combinations of multiple predisposing polymorphisms and their interactions with modifiable factors may result in synergistic effects on the risk of ischemic stroke. These mechanisms are more likely to play a relevant role in younger individuals.
  
  
  METHODS
  The cumulative effect of the 20210A variant of prothrombin gene, the 1691A variant of factor V gene, the TT677 genotype of the methylenetetrahydrofolate reductase (MTHFR) gene, and the epsilon4-carriership of the apolipoprotein (APOE) gene, as well as their interactions with modifiable predisposing factors, were determined in a series of 163 stroke patients aged younger than 45 years and 158 controls.
  
  
  RESULTS
  Odds ratios (ORs) for stroke were 1.73 (95% confidence interval [CI], 1.20 to 2.51) in subjects with 1 polymorphism and 3.00 (95% CI, 1.43 to 6.30) in those with > or =2. Compared with nonsmokers with none of the studied polymorphisms, ORs for stroke were 1.88 (95% CI, 1.18 to 3.00) and 3.55 (95% CI, 1.40 to 8.98) for nonsmokers with 1 and 2 polymorphisms, respectively, and 3.99 (95% CI, 2.00 to 7.96) and 15.99 (95% CI, 4.01 to 63.3) for smokers. Compared with nonhypertensive subjects bearing no polymorphisms, ORs were 1.91 (95% CI, 1.28 to 2.87) and 3.68 (95% CI, 1.64 to 8.26) for nonhypertensive subjects with 1 and 2 polymorphisms, 3.28 (95% CI, 1.01 to 10.7) and 10.79 (95% CI, 1.01 to 115.4) for hypertensive.
  
  
  CONCLUSIONS
  These data suggest a gene-dose effect of the examined prothrombotic and proatherogenic gene variants and a synergistic effect of these polymorphisms and modifiable risk factors in the pathogenesis of cerebral ischemia in young adults.
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
authors.initials: E
authors.lastname: Del Zotto
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.forename: Raffaella
authors.initials: R
authors.lastname: Spezi
authors.forename: Veronica
authors.initials: V
authors.lastname: Vergani
authors.forename: Deodato
authors.initials: D
authors.lastname: Assanelli
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000328:Adult; D001294:Attitude to Health; D002545:Brain Ischemia / Q000453:epidemiology*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006973:Hypertension / Q000453:epidemiology; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics; D012307:Risk Factors; D012907:Smoking / Q000453:epidemiology; D020521:Stroke / Q000453:epidemiology*