The role of ALDH2 and ADH1B polymorphism in alcohol consumption and stroke in Han Chinese

Stroke is the third leading cause of death and the major cause of disability requiring long-term institutionalisation in Taiwan [1]. Epidemiological evidence has shown that heavy drinking is a major risk factor for all stroke subtypes [2].Alcohol metabolism is one of the biological determinants that can significantly influence drinking behaviour and the development of alcoholism and alcohol-related organ damage [3,4]. Most ethanol elimination occurs via oxidation to acetaldehyde and acetate, catalysed principally by alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH), respectively [5]. The genes encoding both enzymes exhibit polymorphism and ethnic variations [6,7]. The allelic variant ALDH2*2 is best known for its role in ethanol metabolism and has been shown to be protective against the development of alcohol dependence [8,9]. Although the ADH1B*2 variant has also been documented as a negative risk factor for developing alcoholism, studies of its effect on drinking behaviour in Asian populations have been inconclusive [10-12]. Among East Asians, including Han Chinese, Japanese and Koreans, 80-90 per cent of individuals carry the variant allele ADH1B*2: this encodes the high-activity ADH1B allozyme which catalyses the oxidation of ethanol to acetaldehyde [4,13]. ADH1B*2 occurs with a much lower frequency in Caucasian and black populations [8]. The variant ALDH2*2 allele encodes the very-low-activity allozyme of ALDH2, impairing the conversion of acetaldehyde to acetate [4]. This inborn error of acetaldehyde metabolism occurs uniquely in about half of East Asians but is rarely seen in other ethnic groups [14].The ALDH2*2 variant has been reported to be involved in alcohol-related diseases, including oropharyngolaryngeal, oesophageal and stomach cancer,[15] colorectal cancer,[16] breast cancer,[17] asthma[18] and myocardial infarction [19,20]. Recently, the ALDH2 polymorphism has been found to contribute to variations in the efficacy of nitroglycerin treatm