Fujihara Junko, Fujii Yoshimi, Agusa Tetsuro, Kunito Takashi, Yasuda Toshihiro, Moritani Tamami, Takeshita Haruo
Department of Legal Medicine, Faculty of Medicine, Shimane University, Izumo, Shimane, Japan.
Toxicol Appl Pharmacol. 2009 Jan 1;234(1):41-6. doi: 10.1016/j.taap.2008.09.026. Epub 2008 Oct 11.
Human arsenic (+3 oxidation state) methyltransferase (AS3MT) is known to catalyze the methylation of arsenite, and intronic single-nucleotide polymorphisms (SNPs: G7395A, G12390C, T14215C, T35587C, and G35991A) in the AS3MT gene were shown to be related to inter-individual variation in the arsenic metabolism. In the present study, the genotyping for these SNPs was developed using the polymerase chain reaction and restriction fragment length polymorphism technique. Applying this method, the genotype distribution among the Ovambo, Turkish, Mongolian, Korean, and Japanese populations was investigated, and our results were compared with those from other studies. G7395, G12390, T35587, and A35991 were predominant among the five populations in our study. However, a previous study in Argentina, C12390 and G35991 showed the highest allele frequency among the eight populations studied in other studies. The dominant allele of T14215C differed among populations: the T14215 allele was predominant in Argentina, the allele frequency of C14215 was higher than that of T14215 among Turks, Mongolians, Europeans, and American ancestry. In Korea and Japan, similar allele frequencies were observed in T14215 and C14215. Higher allele frequencies were observed in haplotype G7395/G12390/C14215/T35587 with frequencies of 0.40 (Turks), 0.28 (Mongolians), and 0.23 (Koreans). On the other hand, the allele frequency for G7395/G14215/T35587/A35991 was the highest among the Ovambos (0.32), and the frequency for G7395/G12390/C35587/G35991 was the highest among the Japanese (0.27). It is noteworthy that the Japanese haplotype differs from that of the Koreans and Mongolians, which indicates the importance of investigating other intronic polymorphisms in AS3MT, especially in Asians.
已知人类砷（+3氧化态）甲基转移酶（AS3MT）可催化亚砷酸盐的甲基化，并且AS3MT基因中的内含子单核苷酸多态性（SNPs：G7395A、G12390C、T14215C、T35587C和G35991A）与砷代谢的个体间差异有关。在本研究中，利用聚合酶链反应和限制性片段长度多态性技术对这些SNPs进行基因分型。应用该方法，调查了奥万博人、土耳其人、蒙古人、韩国人和日本人种群中的基因型分布，并将我们的结果与其他研究的结果进行比较。在我们研究的五个种群中，G7395、G12390、T35587和A35991占主导地位。然而，之前在阿根廷进行的一项研究显示，在其他研究的八个种群中，C12390和G35991的等位基因频率最高。T14215C的优势等位基因在不同种群中有所不同：T14215等位基因在阿根廷占主导地位，在土耳其人、蒙古人、欧洲人和有美国血统的人群中，C14215的等位基因频率高于T14215。在韩国和日本，T14215和C14215的等位基因频率相似。单倍型G7395/G12390/C14215/T35587的等位基因频率较高，在土耳其人、蒙古人和韩国人中的频率分别为0.40、0.28和0.23。另一方面，G7395/G14215/T35587/A35991的等位基因频率在奥万博人中最高（0.32），G7395/G12390/C35587/G35991的频率在日本人中最高（0.27）。值得注意的是，日本人的单倍型与韩国人和蒙古人的不同，这表明研究AS3MT中其他内含子多态性的重要性，尤其是在亚洲人中。
