title: ALDH2*2 but not ADH1B*2 is a causative variant gene allele for Asian alcohol flushing after a low-dose challenge: correlation of the pharmacokinetic and pharmacodynamic findings.
abstract: OBJECTIVE
  It has been well documented that variant alleles of both ADH1B*2 of alcohol dehydrogenase (ADH) and ALDH2*2 of aldehyde dehydrogenase (ALDH) protect against the development of alcoholism in East Asians. However, it remains unclear whether ADH1B*2 contributes significantly toward the accumulation of systemic blood acetaldehyde and whether it plays a critical role in the alcohol flushing reaction.
  
  
  METHODS
  Sixty-one adult Han Chinese men were recruited and divided into six combinatorial genotypic groups: ALDH2*1/*1-ADH1B*1/*1 (12), ALDH2*1/*1-ADH1B*1/*2 (11), ALDH2*1/*1-ADH1B*2/*2 (11); ALDH2*1/*2-ADH1B*1/*1 (9), ALDH2*1/*2-ADH1B*1/*2 (9), and ALDH2*1/*2-ADH1B*2/*2 (9). After ingesting 0.3 g/kg of alcohol, blood ethanol, acetaldehyde, and acetate concentrations, as well as the facial skin blood flow (FSBF) and pulse rate were measured for 130 min.
  
  
  RESULTS
  The ALDH2*1/*2 heterozygotes carrying three ADH1B allelotypes showed significantly higher peak levels and areas under the concentration curve (AUCs) of the blood acetaldehyde as well as significantly greater increases in the peak pulse rate and peak FSBF compared with the ALDH2*1/*1 homozygotes. However, no significant differences in peak levels and AUCs of blood ethanol, acetaldehyde or acetate, or the peak cardiovascular responses, were found between the ADH1B allelotypes carrying ALDH2*1/*1 or between those with ALDH2*1/*2. Partial correlation analyses showed that peak blood acetaldehyde, rather than the blood ethanol or acetate, was correlated significantly with the peak responses of pulse rate and FSBF.
  
  
  CONCLUSIONS
  Findings indicate that ALDH2*2, rather than ADH1B2*2, is a causal variant allele for the accumulation of blood acetaldehyde and the resultant facial flushing during low alcohol consumption.
authors.affiliation: aDepartment of Neurology, Tri-Service General Hospital bDepartment of Biochemistry, National Defense Medical Center, Taipei cDepartment of Psychiatry, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City dDepartment of Nursing, Chang Gung University of Science and Technology, Taoyuan, Taiwan.
authors.forename: Giia-Sheun
authors.initials: GS
authors.lastname: Peng
authors.forename: Yi-Chyan
authors.initials: YC
authors.lastname: Chen
authors.forename: Ming-Fang
authors.initials: MF
authors.lastname: Wang
authors.forename: Ching-Long
authors.initials: CL
authors.lastname: Lai
authors.forename: Shih-Jiun
authors.initials: SJ
authors.lastname: Yin
mesh_terms: D000079:Acetaldehyde / Q000097:blood; D000085:Acetates / Q000097:blood; D000426:Alcohol Dehydrogenase / Q000235:genetics*; D000428:Alcohol Drinking / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D044466:Asian People / Q000235:genetics*; D000431:Ethanol / Q000097:blood / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D055815:Young Adult
chemical_list: D000085:Acetates; D000431:Ethanol; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde