Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American Indian populations: detection of new ALDH2 alleles.

Genetic deficiency of the mitochondrial aldehyde dehydrogenase (ALDH2) is frequent in Asian peoples where it is an important factor negatively regulating drinking behavior. To obtain additional information on gene geography of known ALDH2 alleles, and look for new variants, ALDH2 genes were evaluated in a Chinese population from Taiwan, a Yakut population of Siberia, and in five North American Indian populations. A novel approach based on a single-strand conformation polymorphism assay, and polymerase chain reaction-directed mutagenesis was developed for genotyping. In the Taiwan Chinese population, the ALDH2(2) allele frequency was 0.319 +/- 0.025, and this allele was not detected in the Yakut population nor in the five North American Indian populations. However, a new allele, ALDH2(3), was detected in Pima Indians at a frequency of 0.044 +/- 0.022, and this allele was also observed in 1 of 49 Pueblo samples. ALDH2(3) is a silent transition 1464 G-->A, and it possibly has a wide distribution among North American Indians. A new subtype of the ALDH2(2) allele, designated as ALDH2(2Taiwan), was found in 1 of 174 Chinese from Taiwan. ALDH2(2Taiwan) is characterized by two G-->A transitions at bases 1486 and 1510, resulting in Glu-->Lys substitutions at both the 479 and 487 positions. Thus, this second nonconservative ALDH2 substitution occurs within the sequence of the already inactive ALDH2(2) allele.