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 negative ly regulating drinking behavior. To obtain additional information on g ene geography of known ALDH2 alleles, and look for new variants, ALDH2 genes were evaluated in a Chinese population from Taiwan, a Yakut pop ulation of Siberia, and in five North American Indian populations. A n ovel 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 fre quency was 0.319 +/- 0.025, and this allele was not detected in the Ya kut population nor in the five North American Indian populations. Howe ver, a new allele, ALDH2(3), was detected in Pima Indians at a frequen cy of 0.044 +/- 0.022, and this allele was also observed in 1 of 49 Pu eblo samples. ALDH2(3) is a silent transition 1464 G --> A, and it pos sibly has a wide distribution among North American Indians. A new subt ype 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 s ubstitutions at both the 479 and 487 positions. Thus, this second nonc onservative ALDH2 substitution occurs within the sequence of the alrea dy inactive ALDH2(2) allele.