Mrozikiewicz P M, Cascorbi I, Brockmöller J, Roots I
Institute of Clinical Pharmacology, Charité, Humboldt University of Berlin, Germany.
Clin Pharmacol Ther. 1996 Apr;59(4):376-82. doi: 10.1016/S0009-9236(96)90104-6.
The frequency of various genotypes of arylamine N-acetyltransferase (NAT2) was investigated in 248 Polish unrelated children. Allele-specific polymerase chain reaction (PCR) was applied for mutation at 341 nucleotide (nt) of NAT2 coding sequence and PCR/restriction fragment length polymorphism for the other mutations. Genotypes coded for slow acetylation in 62.9% (56.6% to 68.9%). The frequency of specific NAT2 alleles was *4 (wild-type), 22.0%; *5A (341C, 481T), 5.2%; *5B (341C, 481T, 803G), 33.1%; *5C (341C, 803G), 6.0%; *6A (282T, 590A), 30.0%; *7B (282T, 857A), 3.4%; and *12A (803G), 0.2%. No mutations were found at 191, 434, and 845 nt. By a molecular-genetic procedure, genotypes *4/*6A were confirmed not to mask *6B/*13 (590A/282T). *6B and *13 were absent in a composite sample representative of 826 alleles (95% confidence limits, 0% to 0.45%). Five cases of genotype-phenotype discrepancy were sequenced and their mutation allocation confirmed; 21 further genotypes were confirmed by sequencing. This first evaluation of NAT2 genes among a Slavic population should provide a basis for clinical and epidemiologic investigations of NAT2 in the Polish population.
对248名波兰非亲属儿童的芳胺N - 乙酰基转移酶（NAT2）各种基因型的频率进行了研究。采用等位基因特异性聚合酶链反应（PCR）检测NAT2编码序列第341个核苷酸（nt）处的突变，其他突变则采用PCR/限制性片段长度多态性方法检测。编码慢乙酰化的基因型占62.9%（56.6%至68.9%）。特定NAT2等位基因的频率分别为：*4（野生型），22.0%；*5A（341C，481T），5.2%；*5B（341C，481T，803G），33.1%；*5C（341C，803G），6.0%；*6A（282T，590A），30.0%；7B（282T，857A），3.4%；12A（803G），0.2%。在第191、434和845 nt处未发现突变。通过分子遗传学方法，证实基因型4/6A不会掩盖6B/13（590A/282T）。在代表826个等位基因的混合样本中未发现6B和13（95%置信区间，0%至0.45%）。对5例基因型 - 表型不一致的病例进行了测序并确认了突变定位；另外21种基因型通过测序得到确认。对斯拉夫人群中NAT2基因的首次评估应为波兰人群中NAT2的临床和流行病学研究提供依据。
