Hein David W, Fakis Giannoulis, Boukouvala Sotiria
Department of Pharmacology and Toxicology, University of Louisville Health Sciences Center, Louisville, Kentucky, USA.
Department of Molecular Biology and Genetics, Democritus University of Thrace, Alexandroupolis, Greece.
Pharmacogenet Genomics. 2018 Oct;28(10):238-244. doi: 10.1097/FPC.0000000000000350.
The arylamine N-acetyltransferase (NAT) nomenclature committee assigns functional phenotypes for human arylamine N-acetyltransferase 1 (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 NAT110 and NAT111 alleles were not provided owing to a lack of consensus. Phenotypic inconsistencies observed among various studies for NAT110 and NAT111 may be owing 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, and 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 NAT110 and NAT111 as 'increased-activity' alleles. Some NAT1 variants (e.g. NAT114, NAT117, and NAT122) may be designated as 'decreased-activity' alleles and other NAT1 variants (e.g. NAT115 and NAT119) may be designated as 'no-activity' alleles compared with the NAT14 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 NAT2 alleles.
芳胺N - 乙酰基转移酶（NAT）命名委员会在确定科学文献已达成共识的情况下，为人类芳胺N - 乙酰基转移酶1（NAT1）等位基因指定功能表型。在最近的命名更新中，委员会宣布由于缺乏共识，未提供NAT110和NAT111等位基因的功能表型。NAT110和NAT111在各种研究中观察到的表型不一致可能是由于不同组织之间等位基因表达的差异、基因分型检测的局限性（大多依赖于不涉及直接DNA测序的技术）、所使用的重组蛋白表达系统（细菌、酵母和哺乳动物细胞系）的差异和/或人类NAT1蛋白已知的固有不稳定性，这需要非常小心地处理天然和重组细胞裂解物。最近的三项研究提供了一致的证据，证明NAT110和NAT111作为“活性增加”等位基因的功能表型的机制基础。与NAT14参考等位基因相比，一些NAT1变体（如NAT114、NAT117和NAT122）可能被指定为“活性降低”等位基因，而其他NAT1变体（如NAT115和NAT119）可能被指定为“无活性”等位基因。我们建议停止对NAT1等位基因使用“快速”和“缓慢”乙酰化酶的表型命名，尽管这些命名对于NAT2等位基因仍然非常合适。
