title: The ALDH2 rs671 polymorphism affects post-stroke epilepsy susceptibility and plasma 4-HNE levels.
abstract: Recent studies have demonstrated the protective effect of mitochondrial aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases. Increased levels of the potential ALDH2 substrate 4-hydroxynonenal (4-HNE) are involved in myocardial/cerebral ischemia accompanied by a high level of oxidative stress. In this investigation, we first performed a case-control study to explore the potential association of ALDH2 rs671 polymorphism and post-stroke epilepsy (PSE). Then, we performed an in vitro study to determine whether the overexpression of ALDH2 could decrease the level of oxidative stress and the apoptosis ratio induced by 4-HNE. There was a significant difference in the distribution of the allele and genotype frequencies of the rs671 polymorphism between PSE patients and ischemic stroke (IS) patients. Individuals with the rs671 A allele showed significantly higher levels of plasma 4-HNE. The overexpression of ALDH2 partially blocked the increased levels of malondialdehyde (MDA), reactive oxygen species (ROS) and apoptosis ratio induced by 4-HNE and also partially restored the ALDH2 activity in PC12 cells; these effects were reversed in the presence of εV1-2. Our results suggest that the ALDH2 rs671 polymorphism is associated with PSE susceptibility and affects the 4-HNE levels. Targeting ALDH2 might be a useful strategy for the treatment or prevention of PSE.
authors.affiliation: Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Heng
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurology, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Zhi
authors.initials: Z
authors.lastname: Song
authors.affiliation: Department of Central Laboratory, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Guo-Ping
authors.initials: GP
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Bi-Kui
authors.initials: BK
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, The Third Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Guo
mesh_terms: D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000447:Aldehydes / Q000097:blood*; D000818:Animals; D017209:Apoptosis; D002545:Brain Ischemia / Q000097:blood / Q000150:complications*; D016022:Case-Control Studies; D002470:Cell Survival; D004827:Epilepsy / Q000097:blood / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress; D016716:PC12 Cells; D020641:Polymorphism, Single Nucleotide; D051381:Rats; D012307:Risk Factors
chemical_list: D000447:Aldehydes; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; C027576:4-hydroxy-2-nonenal