Haplotype analysis at the alcohol dehydrogenase gene region in New Zealand Māori.

Alcohol response is a genetically influenced trait, and there is significant variation in the patterns of alcohol consumption between Māori and Caucasians in New Zealand. Previous studies have found that a variant of the alcohol dehydrogenase (ADH) gene (ADH1B*47His) is associated with protection against alcohol dependence in Māori. Here we extend our investigation of the ADH genes, hypothesising a different haplotype signature in Maori compared to Caucasians. We analysed nine single nucleotide polymorphisms (SNPs) spanning a 500-kb region on chromosome 4q surrounding the ADH1B variant and several other alcohol-metabolising genes (ADH 4, 5, 6, 7). Genotyping was carried out on 47 unrelated Māori individuals, and allele frequencies were compared to the Caucasian population. Large differences in minor allele frequencies were observed between Māori and Caucasian populations for six SNPs (P < 0.01). There was also strong linkage disequilibrium (LD) observed among SNP alleles in Maori indicating the presence of extended ancestral haplotype blocks (P < 0.01). Our results suggest that the Māori population has a different haplotype signature at the ADH gene region compared to Caucasians. These findings probably reflect the unique gene flow history of this genomic region in Maori and should be beneficial for designing future genetic association studies of alcohol-response traits and associated disorders in Polynesians.