Xingyang Yi1, Jing Lin2, Chun Wang1, Qiang Zhou3. 1. Department of Neurology, The People's Hospital of Deyang City, Deyang, Sichuan, China. 2. Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China. Electronic address: 22350277@qq.com. 3. Department of Neurology, The Third Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang, China.
Abstract
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.
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 strokepatients. 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. CYP2C8rs17110453 CC, EPHX2rs751141 GG, and CYP4A11rs9333025 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.
Authors: Nuria P Torres-Aguila; Caty Carrera; Elena Muiño; Natalia Cullell; Jara Cárcel-Márquez; Cristina Gallego-Fabrega; Jonathan González-Sánchez; Alejandro Bustamante; Pilar Delgado; Laura Ibañez; Laura Heitsch; Jerzy Krupinski; Joan Montaner; Joan Martí-Fàbregas; Carlos Cruchaga; Jin-Moo Lee; Israel Fernandez-Cadenas Journal: J Stroke Date: 2019-09-30 Impact factor: 6.967
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