Cumulative effect of predisposing genotypes and their interaction with modifiable factors on the risk of ischemic stroke in young adults.
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.
Pezzini
Alessandro
A
Clinica Neurologica, Università degli Studi di Brescia, P.le Spedali Civili, 1, 25100 Brescia, Italia. ale_pezzini@hotmail.com
Grassi
Mario
M
Del Zotto
Elisabetta
E
Archetti
Silvana
S
Spezi
Raffaella
R
Vergani
Veronica
V
Assanelli
Deodato
D
Caimi
Luigi
L
Padovani
Alessandro
A
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*