Synergistic Effect of Apolipoprotein E Polymorphisms and Cigarette Smoking on Risk of Ischemic Stroke in Young Adults

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Abstract
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 ε4 allele and ε34 genotype was slightly higher in cases than in controls (0.125 versus 0.071 and 0.242 versus 0.136, respectively). Carriers of the ε34 genotype and ε4 allele were associated with an increased risk of stroke on multivariate analysis compared with the ε33 genotype and non-ε4 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 ε33 genotype, nonsmokers with the ε34 genotype, and smokers with the ε34 genotype, respectively, compared with nonsmokers with the ε33 genotype. Similar results were obtained when ε4 carriers and non-ε4 carriers were compared in the same interaction model. No significant interaction between APOE and hypertension was found. Conclusions— In young adults, the APOE ε4 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.