Effects of Genetic Polymorphisms of the Human PNP, CYT19 and GSTO1 on Individual Variation of Urinary Arsenic Metabolites after Oyster Ingestion

• Main Authors: Yeh-Hsin Chen, 陳業欣
• Other Authors: 黃耀輝
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/86761484438103103404

碩士 === 國立臺灣大學 === 職業醫學與工業衛生研究所 === 94 === Abstract Food and drinking water are the major exposure routes of arsenic among the general population. In general, it was believed that the toxicity of inorganic arsenic was greater than organic arsenic. Up to now, inorganic arsenic is more thoroughly studied than organic arsenic. Consequently, the metabolism of organic arsenic has not been closely unveilded yet. However, there are considerable variations in the metabolism of inorganic and organic arsenic among individuals. Factors which have been shown to influence the methylation of arsenic include age, gender, ethnics, form of arsenic administered, environmental factors and genetic polymorphism, etc. The goal of the present study is to explore the effects of genetic polymorphisms of the human PNP, CYT19 and GSTO1 on the variation of arsenic metabolic rate among individuals, and the correlation between genetic polymorphism and the variation of urinary arsenic metabolites after oyster ingestion. Fifty one study subjects were recruited from the past three dietary control studies. During the one-week dietary control study, the study subjects ate the same food stuffs containing no seafood in all meals to exclude the unexpected seafood uptake, except for the ingestion of designated amount of oyster on the fourth day. First morning-voided urine samples of the study subjects were collected for 7 consecutive days and analyzed by HPLC-HG-AAS and HPLC-ICP-MS for urinary arsenic species, i.e. As3+, As5+, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Then the blood samples of study subjects were collected for analyzing the genetic polymorphisms of the human PNP, CYT19 and GSTO1. In general, DMA was the major urine metabolite, and its concentration reached the highest level on the first day after oyster ingestion and gradually decreased latter. The daily fluctuation of As3+ was similar to that of DMA. The DMA metabolic rate was categorized into three levels, i.e. fast (n=28), medium (n=19) and slow (n=4) groups, respectively, according to the day on which the urinary DMA concentrations reached the highest levels among these days after oyster ingestion. Based on this, it was concluded that there was difference in the metabolic rate of organic arsenic among study subjects. The mean age of the fast metabolic group, 28.3±1.0 years, was significantly greater than that of the slow metabolic group, 25.7±1.6 years. SNP (G > C) in intron6 of CYT19 gene was positively associated with DMA metabolic rate (p=0.027) as compared to wild-type gene. The relationships of age and SNP (G > C) in intron6 of CYT19 with either maximum or cumulative DMA increased concentration were explored by multiple linear regression. Data showed that the older the subjects are, the less the cumulative DMA increased concentration are (β=-3.97). In addition, the maximum and the cumulative DMA increased concentrations of study subjects who had SNP (G > C) in intron6 of CYT19 gene were higher than subjects whose genes were wild-type (β=4.68, β=1.67, respectively,) although both of them were not significant statistically. According to the above, age and SNP (G > C) in intron6 of CYT19 were the factors that had influence on the variation of DMA metabolic rate and then caused the difference in urinary DMA metabolite among study subjects.