title: ALDH2---The Genetic Polymorphism and Enzymatic Activity Regulation: Their Epidemiologic and Clinical Implications.
abstract: BACKGROUND
  The human aldehyde dehydrogenase 2 (ALDH2) is the most effective enzyme in the detoxification of alcohol metabolite acetaldehyde. The ALDH2*2 mutation is caused by a single nucleotide substitution which results in a nearly inactive form of ALDH2 enzyme. The ALDH2 genotype has been used as a surrogate of alcohol to get causal inferences of alcohol in related diseases implementing Mendelian randomization approach. In addition, ALDH2 enzyme has significant effect on different diseases, indicating the potential therapeutic value of ALDH2 regulators including both activators like Alda-1 and inhibitors such as daidzin and daidzein.
  
  
  OBJECTIVE
  In this review, we aim to systematically discuss the implications of ALDH2 genotype and ALDH2 enzyme regulators, highlighting their epidemiological and clinical importance, respectively.
  
  
  CONCLUSIONS
  ALDH2 polymorphism is shown to be a genetic instrument for alcohol use in Mendelian randomization analysis. ALDH2 regulators exhibit potential therapeutic value as the important roles of ALDH2 in various diseases. Both the genetic polymorphism and enzyme activity regulation of ALDH2 are of great importance to their epidemiologic and clinical applications.
authors.affiliation: Department of Emergency, Qilu Hospital, Shandong University, Jinan, China.|Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.|Institute of Emergency and Critical Care Medicine, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling & Function Research, Chinese Ministry of Education & Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Emergency, Qilu Hospital, Shandong University, Jinan, China.|Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.|Institute of Emergency and Critical Care Medicine, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling & Function Research, Chinese Ministry of Education & Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Jiali
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Emergency, Qilu Hospital, Shandong University, Jinan, China.|Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.|Institute of Emergency and Critical Care Medicine, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling & Function Research, Chinese Ministry of Education & Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Mengyang
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Emergency, Qilu Hospital, Shandong University, Jinan, China.|Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.|Institute of Emergency and Critical Care Medicine, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling & Function Research, Chinese Ministry of Education & Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
authors.affiliation: Department of Emergency, Qilu Hospital, Shandong University, Jinan, China.|Chest Pain Center, Qilu Hospital, Shandong University, Jinan, China.|Institute of Emergency and Critical Care Medicine, Shandong University, Jinan, China.|Key Laboratory of Emergency and Critical Care Medicine of Shandong Province, Qilu Hospital, Shandong University, Jinan, China.|Key Laboratory of Cardiovascular Remodeling & Function Research, Chinese Ministry of Education & Chinese Ministry of Public Health, Qilu Hospital, Shandong University, Jinan, China.
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000428:Alcohol Drinking; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D020022:Genetic Predisposition to Disease; D006801:Humans; D020641:Polymorphism, Single Nucleotide
chemical_list: C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: ALDH2 activator; ALDH2 inhibitor; Aldehyde dehydrogenase 2 (ALDH2); Mendelian
  randomization; genetic polymorphism; observational epidemiology