Agúndez J A, Olivera M, Martínez C, Ladero J M, Benítez J
Department of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.
Pharmacogenetics. 1996 Oct;6(5):423-8.
The prevalence and distribution of seven point mutations at the coding region of the highly polymorphic NAT2 gene were studied in 1008 chromosomes from healthy Spanish subjects. Most of the genes studied (78.4%) had one or more mutations, distributed in seventeen allelic variants of the NAT2 gene. Three alleles were present at high frequencies, namely NAT25B (41.6%), NAT26A (23.6%) and NAT24 (21.6%). The frequencies for the rest of alleles were: NAT212A (2.5%), NAT26B (2.0%), NAT213 (1.9%), NAT25A (1.5%), NAT27B (1.2%), NAT212C (1.0%), NAT25C (0.8%), NAT214C (0.8%), NAT214A (0.6%), NAT25D (0.3%), NAT212B (0.2%), and NAT214D (0.1%). In addition, we identified two new allelic variants with mutations at 191A + 341C + 803G (0.1%) and 282T + 590A + 803G (0.3%) which to our knowledge are described here for the first time. No other combination of mutations was identified, including the previously described allelic variants NAT214B, NAT214E, NAT25E and NAT2*7A. The phenotype predictive capacity of simplified PCR tests including analyses for mutations at 341C and 590A, and more sophisticated tests analysing seven mutations revealed that, in the population studied, the analysis of these two mutations is enough to predict as rapid acetylators over 99.5% subjects with two rapid genes, and about 94% subjects with one rapid gene. Given a prevalence of poor acetylators of about 55% subjects, the simplified analysis would predict the phenotype in about 97.5% subjects.
在来自健康西班牙受试者的1008条染色体中，研究了高度多态性的NAT2基因编码区七个点突变的流行情况和分布。研究的大多数基因（78.4%）有一个或多个突变，分布在NAT2基因的17个等位基因变体中。三个等位基因高频存在，即NAT25B（41.6%）、NAT26A（23.6%）和NAT24（21.6%）。其余等位基因的频率为：NAT212A（2.5%）、NAT26B（2.0%）、NAT213（1.9%）、NAT25A（1.5%）、NAT27B（1.2%）、NAT212C（1.0%）、NAT25C（0.8%）、NAT214C（0.8%）、NAT214A（0.6%）、NAT25D（0.3%）、NAT212B（0.2%）和NAT214D（0.1%）。此外，我们鉴定出两个新的等位基因变体，分别在191A + 341C + 803G（0.1%）和282T + 590A + 803G（0.3%）位点发生突变，据我们所知，这是首次在此处描述。未鉴定出其他突变组合，包括先前描述的等位基因变体NAT214B、NAT214E、NAT25E和NAT2*7A。包括对341C和590A位点突变分析的简化PCR检测以及分析七个突变的更复杂检测的表型预测能力表明，在所研究的人群中，对这两个突变的分析足以预测超过99.5%具有两个快速基因的受试者以及约94%具有一个快速基因的受试者为快速乙酰化者。鉴于约55%的受试者为慢乙酰化者，简化分析可预测约97.5%受试者的表型。
