Synergistic Effect of Apolipoprotein E Polymorphisms and Cigarette Smoking on Risk of Ischemic Stroke in Young Adults.
Pezzini, Alessandro MD; Grassi, Mario PhD; Del Zotto, Elisabetta MD; Bazzoli, Elena MD; Archetti, Silvana PhD; Assanelli, Deodato MD; Akkawi, Nabil Maalikjy MD; Albertini, Alberto MD; Padovani, Alessandro MD, PhD
35(2):438-442, February 2004.
(Format: HTML, PDF)
Background and Purpose-: The effect of apolipoprotein E (APOE) polymorphisms on stroke risk may be influenced by the coexistence of modifiable predisposing conditions. We explored the interactions of APOE genotypes and conventional risk factors in a case-control study of young adults with cerebral infarct.
Methods-: We analyzed 124 consecutive patients (age, 34.7 /-7.3 years) and 147 age- and sex-matched controls. APOE genotypes were determined by restriction fragment-length polymorphism analysis.
Results-: The prevalence of the [epsilon]4 allele and [epsilon]34 genotype was slightly higher in cases than in controls (0.125 versus 0.071 and 0.242 versus 0.136, respectively). Carriers of the [epsilon]34 genotype and [epsilon]4 allele were associated with an increased risk of stroke on multivariate analysis compared with the [epsilon]33 genotype and non-[epsilon]4 carriers, respectively (odds ratio [OR], 2.29; 95% confidence interval [CI], 1.10 to 4.76; and OR, 2.27; 95% CI, 1.13 to 4.56). ORs for stroke were 2.99 (95% CI, 1.64 to 5.45), 2.69 (95% CI, 1.25 to 5.77), and 5.39 (95% CI, 1.59 to 18.30) for smokers with the [epsilon]33 genotype, nonsmokers with the [epsilon]34 genotype, and smokers with the [epsilon]34 genotype, respectively, compared with nonsmokers with the [epsilon]33 genotype. Similar results were obtained when [epsilon]4 carriers and non-[epsilon]4 carriers were compared in the same interaction model. No significant interaction between APOE and hypertension was found.
Conclusions-: In young adults, the APOE [epsilon]4 allele and cigarette smoking act synergistically, increasing an individual's propensity to have a cerebral ischemic event. This finding may help in determining an individual's predisposition to stroke and more targeted preventive interventions.
(C) 2004 American Heart Association, Inc.