Functional expression of human arylamine N-acetyltransferase NAT1*10 and NAT1*11 alleles: a minireview

摘要

The arylamine N-acetyltransferase (NAT) nomenclature committee assigns functional phenotypes for human NAT1 alleles in those instances in which the committee determined a consensus has been achieved in the scientific literature. In the most recent nomenclature update, the committee announced that functional phenotypes for NAT1*10 and NAT1*11 alleles were not provided due to lack of consensus. Phenotypic inconsistencies observed among various studies for NAT1*10 and NAT1*11 may be due to variable allelic expression among different tissues, the limitations of the genotyping assays (which mostly relied on techniques not involving direct DNA sequencing), the differences in recombinant protein expression systems used (bacteria, yeast, mammalian cell lines) and/or the known inherent instability of human NAT1 protein which requires very careful handling of native and recombinant cell lysates. Three recent studies provide consistent evidence of the mechanistic basis underlying the functional phenotype of NAT1*10 and NAT1*11 as “increased-activity” alleles. Some NAT1 variants (e.g. NAT1*14, NAT1*17, and NAT1*22) may be designated as “decreased-activity” alleles and other NAT1 variants (e.g., NAT1*15 and NAT1*19) may be designated as “no-activity” alleles compared to the NAT1*4 reference allele. We propose that phenotypic designations as “rapid” and “slow” acetylator should be discontinued for NAT1 alleles, although these designations remain very appropriate for N-acetyltransferase 2 (NAT2) alleles.