The Genetics of Human Alcohol Metabolism in the New Zealand Population

Abstract

A DNA bank of samples from individuals of some of the ethnic groups comprising the New Zealand Population has been constructed. These ethnic groups include Caucasians, Orientals, Maori, Cook Island Maori and Western Samoans. This DNA bank has been surveyed for genetic variation in liver detoxication systems involved in the removal of alcohol after consumption. Direct sequencing data have been gathered which show that the ADH 2-2 allele is present at a significant frequency in the New Zealand Polynesian group. The Polynesian ADH 2-2 allele frequency observed (0.46) is intermediate between that of the New Zealand Caucasian group (0.03, p<0.001) and the New Zealand Oriental group (0.76, p<0.005). The ALDH 2-2 allele was not observed in either the New Zealand Polynesian or Caucasian Groups, although the Oriental ALDH 2-2 allele frequency (0.21) observed was in accord with expectations. The ADH 2-3 allele was not observed in any of the groups surveyed. These data are novel, and the publication elsewhere (Marshall et al., 1994a, Marshall and Chambers, 1994a) represents the first report of ADH 2-2 and ALDH 2-2 allele frequencies in Polynesians. DNA samples have been collected from alcoholic patients of the Caucasian and Maori ethnic groups. These have also been surveyed for the ADH 2-2 and ALDH 2-2 allele by direct sequencing. The ADH 2-2 allele frequency has been observed to be significantly lower in Maori alcoholic patients (0.15, p<0.001) when compared with the control population. A similar reduction in ADH 2-2 allele frequency was not observed in the Caucasian alcoholic patients surveyed (ADH 2-2 allele frequency = 0.03, p>0.10). These data are similar to those presented by other workers (for example Chao et al., 1994) but represent the first report of a reduction in ADH 2-2 allele frequencies related to alcoholism in a non-Oriental population (Marshall et al,1994b, Marshall and Chambers, 1994b). Nucleotide substitution rates have been calculated for the sequence data from ADH 2 and ALDH 2. A total of 33,904 nucleotides were examined, giving substitution rates of 0/11,728 for non-degenerate sites, 0/6,118 for two-fold degenerate sites, 0/4,290 for four-fold degenerate sites and 8/11768 for intron sites. These values are similar to those reported for other human genes and much lower than those observed in Drosophila (Li and Sadler, 1991). As well as these human data, DNA sequence has been obtained for the black handed spider monkey (Ateles geoffroyi ) ADH 2 homologue and this has been compared with the sequence of human ADH 1, ADH 2 and ADH 3 and baboon ADH β. The spider monkey ADH 2 homologue was found to share much greater similarity to the human ADH 2 (1/68) than the baboon ADH β (2/68), despite humans and baboons being more closely related than humans and spider monkeys. These data allow the following conclusions: the ADH 2-2 allele is associated with some reduction in the risk of developing alcoholism, possibly by inducing a form of behavioural avoidance; ADH 2 and ALDH 2 have a low level of nucleotide substitution when compared with the rate in Drosophila, in accord with other human proteins; Polynesians are probably descended from an Oriental founder population in a region of Asia with high frequencies of the ADH 2-2 allele and low frequencies or an absence of the ALDH 2-2 allele.