Published Online
on January 15, 2004

A more recent version of this article appeared on February 1, 2004

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Submitted on October 2, 2003
Accepted on October 24, 2003

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

Alessandro Pezzini MD^*; Mario Grassi PhD; Elisabetta Del Zotto MD; Elena Bazzoli MD; Silvana Archetti PhD; Deodato Assanelli MD; Nabil Maalikjy Akkawi MD; Alberto Albertini MD; and Alessandro Padovani MD, PhD

From Clinica Neurologica (A.P., E. Del Z., E.B., N.M.A., A.P.), Clinica Cardiologica (D.A.), and III Laboratorio di Analisi, Biotecnologie (S.A., A.A.), Università degli Studi di Brescia, Brescia, and Istituto di Statistica Medica e Biometrie, Università degli Studi di Pavia, Pavia (M.G.), Italia.

^* To whom correspondence should be addressed. E-mail: ale_pezzini{at}hotmail.com.

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 4 allele and 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 34 genotype and 4 allele were associated with an increased risk of stroke on multivariate analysis compared with the 33 genotype and non-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 33 genotype, nonsmokers with the 34 genotype, and smokers with the 34 genotype, respectively, compared with nonsmokers with the 33 genotype. Similar results were obtained when 4 carriers and non-4 carriers were compared in the same interaction model. No significant interaction between APOE and hypertension was found.

Conclusions--In young adults, the APOE 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.

Key words: apolipoproteins • cigarette smoking • polymorphism • risk factors

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