CYP Genetic Variants, CYP Metabolite Levels, and Neurologic Deterioration in Acute Ischemic Stroke in Chinese Population

• Published in: Journal of stroke and cerebrovascular diseases 2017-05, Vol.26 (5), p.969-978
• Main Authors: Yi, Xingyang, MD, Lin, Jing, MD, Wang, Chun, MSc, Zhou, Qiang, MD
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Asian Continental Ancestry Group - genetics; Biomarkers - blood; Brain Ischemia - diagnosis; Brain Ischemia - enzymology; Brain Ischemia - ethnology; Brain Ischemia - genetics; Cardiovascular; Chi-Square Distribution; China - epidemiology; Cytochrome P-450 CYP2C8 - genetics; Cytochrome P-450 CYP2C8 - metabolism; Cytochrome P-450 CYP4A - genetics; Cytochrome P-450 CYP4A - metabolism; Cytochrome P-450 Enzyme System - genetics; Cytochrome P-450 Enzyme System - metabolism; cytochrome P450; Eicosanoids - blood; Epoxide Hydrolases - genetics; Epoxide Hydrolases - metabolism; Female; Gene Frequency; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Hydroxyeicosatetraenoic Acids - blood; ischemic stroke; Male; Middle Aged; Nerve Degeneration; Neurologic deterioration; Neurology; Odds Ratio; Phenotype; Polymorphism, Single Nucleotide; Prospective Studies; Risk Factors; single nucleotide polymorphisms; Stroke - diagnosis; Stroke - enzymology; Stroke - ethnology; Stroke - genetics; Time Factors
• ISSN: 1052-3057; 1532-8511
• DOI: 10.1016/j.jstrokecerebrovasdis.2016.11.004

Background The mechanisms of neurologic deterioration (ND) are not fully understood. The aim of the present study was to evaluate the relationship between CYP genetic variants and CYP metabolite levels with ND in acute ischemic stroke patients. Methods Eleven single nucleotide polymorphisms (SNPs) of seven CYP genes were genotyped in 396 patients with acute ischemic stroke. The CYP plasma metabolite levels (20-hydroxyeicosatetraenoic acid [HETE], total epoxyeicosatrienoic acids [EETs], and dihydroxyeicosatrienoic acids [DiHETEs]) were also assessed. The primary outcome was ND within 10 days on admission. ND was defined as an increase of two or more points in the National Institutes of Health Stroke Scale score. Results Among 396 patients, 101 patients (25.5%) experienced ND. The plasma levels of 20-HETE and DiHETEs were significantly higher and the EET levels were significantly lower in patients with ND compared to patients without ND. Univariate analyses revealed that old age, diabetes mellitus (DM), higher fasting glucose, and higher hemoglobin A1c (HbA1c) were associated with ND. CYP2C8 rs17110453 CC, EPHX2 rs751141 GG, and CYP4A11 rs9333025 GG were independently associated with ND after adjusting age, DM, fasting glucose, and HbA1c (odds ratio [OR]: 1.60, 95% confidence interval [CI]: 1.02-3.72; OR: 3.01, 95% CI: 1.29-7.13; OR: 2.75, 95% CI: 1.17-6.24, respectively). Also, these polymorphisms were associated with CYP metabolite levels in patients with ND. Conclusions ND is fairly common in acute ischemic stroke. Specific CYP gene SNPs are associated with CYP plasma metabolite levels, which may explain their associations with ND. Further studies are needed to validate our findings.