Acetaldehyde, polymorphisms and the cardiovascular system.
To date, the only genes that have been consistently replicated across racial and ethnic groups to influence alcoholism vulnerability are polymorphisms in the alcohol-metabolizing enzymes, i.e. cytosolic alcohol dehydrogenase 1B (ADH1B) and mitochondrial aldehyde dehydrogenase 2 (ALDH2). Both the variant ADHIB*2 and ALDH2*2 alleles significantly protect against developing alcoholism. The protection has been thought to result from accumulation of acetaldehyde after drinking. Unlike ALDH2*2, direct correlation between ADHI1B*2 and blood acetaldehyde has not been verified. ALDH2*2/*2 homozygosity appeared to almost completely protect against alcoholism, whereas ALDH2* 1/*2 heterozygosity appeared to reduce risk of the disease only about threefold. Direct correlations of blood ethanol and acetaldehyde concentrations, cardiovascular haemodynamic responses, and the subjective perceptions after challenge with low (0.2g/kg) to moderate (0.5g/kg) alcohol in individuals with different ALDH2 genotypes support the notion that full protection against alcoholism byALDH2*2/*2 may derive from either abstinence or deliberate moderation in alcohol consumption due to strong discomfort from physiological and psychological responses caused by persistently elevated blood acetaldehyde after ingestion of a small amount of alcohol, and that the partial protection by ALDH2*1/*2 can be ascribed to significantly lower acetaldehyde build-up in blood and the according adverse reactions.
Yin
Shih-Jiun
SJ
Department of Biochemistry, National Defense Medical Center, 161 Min-Chuan East Road Section 6, Taipei 114, Taiwan.
Peng
Giia-Sheun
GS
D000079:Acetaldehyde / Q000097:blood / Q000378:metabolism* / Q000493:pharmacokinetics / Q000633:toxicity; D000426:Alcohol Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000437:Alcoholism / Q000235:genetics* / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000378:metabolism; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000704:Analysis of Variance; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002849:Chromatography, Gas; D002851:Chromatography, High Pressure Liquid; D015150:Echocardiography, Doppler; D000431:Ethanol / Q000097:blood; D005006:Ethnicity / Q000235:genetics; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D011110:Polymorphism, Genetic; D044469:Racial Groups / Q000235:genetics
D000431:Ethanol; C489332:ADH1B protein, human; D000426:Alcohol Dehydrogenase; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde