Distribution of genetic polymorphism of aldehyde dehydrogenase-2 (ALDH2) in Indonesian subjects

Abstract

Aldehyde dehydrogenase (ALDH) plays a pivotal role in the alcohol metabolism. Decreased activity of ALDH enzyme has more influence on the hypersensitivity to alcohol than of alcohol dehydrogenase. ALDH enzyme exists in several isozymes. Among these isozymes, ALDH2 is a major isozyme that has a very high affinity for acetaldehyde. Recent studies suggested that the deficiency of ALDH2 may be inherited. Functional polymorphism of ALDH2 gene has been observed in a nucleotide of the 487th codon. In the atypical gene, this codon consists of AAA nucleotides for lysine, instead of GAA for glutamic acid in the wild type gene. In this study, we have analyzed the genetic polymorphism of ALDH2 gene among 100 Indonesian students using genomic DNA extracted from hair roots. Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) methods were performed for this purpose. Three oligonucleotide primers were designed for two steps PCR. The reverse primer R was intentionally constructed not to be 100% complementary to the template strand, to generate a restriction site for Eco RI within the variable nucleotide in the PCR product of ALDH2 gene. This study indicates that 70 subjects (70%) have wild type, 29 (29%) atypical heterozygote and only 1 (1%) atypical homozygote ALDH2 alleles. Conclusively, the atypical ALDH2 allele frequency in Indonesians (31/200) is higher than in Caucasoids (only about 5-10%), but less than in Mongoloids (40-50%). This may be due to the diverse ethnics of Indonesian population. (Med J Indones 2002; 11: 135-42)

Keywords: alcohol hypersensitivity, genetic polymorphism, aldehyde dehydrogenase-2 (ALDH2) gene