Abe M, Deguchi T, Suzuki T
Department of Clinical Genetics, Kyushu University, Oita, Japan.
Biochem Biophys Res Commun. 1993 Mar 31;191(3):811-6. doi: 10.1006/bbrc.1993.1289.
Polymorphic N-acetyltransferase (NAT2), which exists in the human liver and metabolizes a wide spectrum of arylamine, is encoded by one gene (NAT2). We have identified the mutations of a fourth NAT2 allele (allele 4) which we previously found in the Japanese population. Compared with allele 1, which expresses a high enzyme activity, allele 4 has 3 nucleotide differences. 2 are missense mutations at nucleotide position (nt) 341 and 803. The other is a silent mutation at the KpnI site. From the result of expression studies of chimeric gene constructs between allele 1 and allele 4 in Chinese hamster ovary cells, nt 341 missense mutation of the allele 4 which causes the Ile-114 to Thr change is responsible for the low enzyme activity of NAT2 protein.
多态性N - 乙酰基转移酶（NAT2）存在于人类肝脏中，可代谢多种芳胺，由一个基因（NAT2）编码。我们已鉴定出先前在日本人群中发现的第四个NAT2等位基因（等位基因4）的突变。与表达高酶活性的等位基因1相比，等位基因4有3个核苷酸差异。其中2个是位于核苷酸位置（nt）341和803处的错义突变。另一个是KpnI位点的沉默突变。通过在中国仓鼠卵巢细胞中对等位基因1和等位基因4之间的嵌合基因构建体进行表达研究的结果表明，等位基因4中导致Ile - 114变为Thr的nt 341错义突变是NAT2蛋白低酶活性的原因。
