Genetic Polymorphisms of ALOX5AP and CYP3A5 Increase Susceptibility to Ischemic Stroke and Are Associated with Atherothrombotic Events in Stroke Patients

• Published in: Journal of stroke and cerebrovascular diseases 2015-03, Vol.24 (3), p.521-529
• Main Authors: Yi, Xingyang, MD, Zhang, Biao, MD, Wang, Chun, MSc, Liao, Duanxiu, MSc, Lin, Jing, MD, Chi, Lifen, MD
• Format: Article
• Language: English
• Subjects: 5-lipoxygenase activating protein; 5-Lipoxygenase-Activating Proteins - genetics; Aged; Aged, 80 and over; Atherosclerosis - diagnosis; Atherosclerosis - enzymology; Atherosclerosis - genetics; Atherosclerosis - mortality; Brain Ischemia - diagnosis; Brain Ischemia - enzymology; Brain Ischemia - genetics; Brain Ischemia - mortality; Cardiovascular; Case-Control Studies; Chi-Square Distribution; China; Cytochrome P-450 CYP3A - genetics; cytochrome P450; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; genetics; GMDR; Humans; Logistic Models; Male; Middle Aged; Multivariate Analysis; Neurology; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Prognosis; Proportional Hazards Models; Recurrence; Risk Factors; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Stroke; Stroke - diagnosis; Stroke - enzymology; Stroke - genetics; Stroke - mortality; Thrombosis - diagnosis; Thrombosis - enzymology; Thrombosis - genetics; Thrombosis - mortality; variants
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2014.09.035

Background The contributions of gene–gene interactions to pathogenesis of stroke remain largely elusive. The present study was designed to investigate the associations between genetic variations and ischemic stroke risk, the roles of gene–gene interactions in ischemic stroke, and their associations with atherothrombotic events. Methods Among 396 patients with ischemic stroke and 378 controls, we examined 8 variants from 5 genes, including ALOX5AP -SG13S32 (rs9551963), SG13S42 (rs4769060), SG13S89 (rs4769874), SG13S114 (rs10507391), EPHX2 G860A (rs751141), CYP2C9*2 C430T (rs1799853), CYP2C9*3 A1075C (rs1057910), and CYP3A5 A6986G (rs776746), using matrix-assisted laser desorption/ionization time of flight mass spectrometry. Gene–gene interactions were determined by the generalized multifactor dimensionality reduction (GMDR) method. All ischemic stroke patients were followed up 12 months for atherothrombotic events, including recurrent ischemic stroke and other vascular events. Results Single-gene variant analysis showed no significant differences in the genotype distributions of the 8 variants between the 2 groups. However, the GMDR analysis showed a significant interaction between rs10507391 and rs776746, in those cases carrying rs10507391 AA and rs776746 GG, the risk of ischemic stroke increased by 2.014 times (95% confidence interval [CI], 1.896-6.299; P  = .006), and the atherothrombotic events occurred more frequently in those patients during follow-up period ( P