Synergistic effect of apolipoprotein E polymorphisms and cigarette smoking on risk of ischemic stroke in young adults

Stroke. 2004 Feb;35(2):438-42. doi: 10.1161/01.STR.0000112973.00867.98. Epub 2004 Jan 15.


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 epsilon4 allele and epsilon34 genotype was slightly higher in cases than in controls (0.125 versus 0.071 and 0.242 versus 0.136, respectively). Carriers of the epsilon34 genotype and epsilon4 allele were associated with an increased risk of stroke on multivariate analysis compared with the epsilon33 genotype and non-epsilon4 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 epsilon33 genotype, nonsmokers with the epsilon34 genotype, and smokers with the epsilon34 genotype, respectively, compared with nonsmokers with the epsilon33 genotype. Similar results were obtained when epsilon4 carriers and non-epsilon4 carriers were compared in the same interaction model. No significant interaction between APOE and hypertension was found.

Conclusions: In young adults, the APOE epsilon4 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.

MeSH terms

  • Adult
  • Apolipoproteins E / genetics*
  • Brain Ischemia / epidemiology*
  • Case-Control Studies
  • Comorbidity
  • Female
  • Genotype
  • Humans
  • Italy / epidemiology
  • Male
  • Multivariate Analysis
  • Odds Ratio
  • Polymorphism, Genetic / genetics*
  • Polymorphism, Restriction Fragment Length
  • Prevalence
  • Risk Assessment
  • Risk Factors
  • Smoking / epidemiology*
  • Stroke / epidemiology*


  • Apolipoproteins E