Association of genetic variation in apolipoprotein E and low density lipoprotein receptor with ischemic stroke in Northern Han Chinese

Background: Ischemic stroke is the end phenotype of a complex interaction between various genetic and environmental factors. Objective: We aimed to explore association of two lipid-relevant genetic variants and conventional risk factors with risk of having ischemic stroke in Northern Han Chinese. Methods: Genotyping was performed in 396 ischemic stroke patients and 396 controls that were all recruited from the four hospitals of Qiqihar city. Data were analyzed using chi(2) test, logistic regression and haplotype analyses. Results: Significant differences were observed for genotype and allele distributions of APOE epsilon 2/epsilon 3/epsilon 4 polymorphism (P<0.001) with epsilon 4 allele conferring a 2.19-fold risky effect (P<0.001), while no statistical differences were found for LDLR C1773T distributions. Haplotype analysis indicated the remarkable differences for haplotypes harboring APOE epsilon 2 or epsilon 4 alleles between cases and controls after the stringent Bonferroni correction. Moreover, all multiple-testing associations remained significant using false discovery rate (FDR) method. Further our multiple logistic regression analysis showed significant associations of hypertension status (OR=5.37, P<0.001) and APOE epsilon 2 (OR=0.45, P<0.001) and epsilon 4 (OR=1.50, P=0.003) alleles with ischemic stroke after controlling confounders, and their correlations with plasma lipid profiles were strengthened by Stratification of alleles and hypertension status combined. Conclusions: Our results not only demonstrated potential interactions of APOE epsilon 2/epsilon 3/epsilon 4 and LDLR C1773T polymorphisms with risk of having ischemic stroke, but also added the evidence of independent role of hypertension and APOE epsilon 2/epsilon 3/epsilon 4 polymorphism in the development of this disorder in Northern Han Chinese. (C) 2008 Elsevier B.V. All rights reserved.