- 期刊
聚氯乙烯工人GST T1，GST M1及CYP2E1基因型與其肝功能之相關研究
The Relationship between the GST T1, GST M1, CYP2E1 Genotype and Abnormal Liver Function in PVC Workers
摘要
Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form chloroethylene oxide (CEO) and chloroactetaldehyde (CAA), both electrophilic metabolites, which may either cause cell damage or are further metabolized and detoxified by glutathione S-transferases (GSTs). This study investigated whether or not the genotypes, CYP2E1, glutathione S-transferase θ (GST T1) and μ (GST M1), correlated the abnormal liver function in vinyl chloride exposed workers. We enrolled 251 workers from 5 polyvinyl chloride plants for this study. The workers who were exposed to VCM were classified into two, high and low exposure groups and the degree of exposure was determined based on their job titles and airborne VCM concentration. The enzyme activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were used as the parameters of liver function. The genotypes, CYP2E1, GST T1 and GST M1, were determined by performing PCR and RFLP on peripheral white blood cell DNA, Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes, CYP2E1, GST T1 and GST M1, among the workers exposed to different levels of VCM. The results obtained showed: (1)at low VCM exposure, the odds ratio (OR) of GST T1 non-null genotype on abnormal ALT was 3.8 (95% CI=1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT; (2)at high VCM exposure, on the other band, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR=4.8, 95% CI=0.6-34.8) but the GST T1 non-null genotype was not associated with abnormal ALT (OR=0.9, 95% CI=0.2-3,8); and (3)multiple logistic regression also showed strong interactions of the VCM exposure to CYP2E1 as well as to the GST T1 genotype. Thus, These observations suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in the biotransformation of VCM, whose effect leads to liver damage.
並列摘要
Vinyl chloride monomer (VCM) is hepatotoxic as well as carcinogenic in humans. There are reports that exposure to VCM seems to induce abnormal liver function, liver fibrosis, cirrhosis, and angiosarcoma of the liver. In vivo, VCM is metabolized by cytochrome P450 2E1 (CYP2E1) to form chloroethylene oxide (CEO) and chloroactetaldehyde (CAA), both electrophilic metabolites, which may either cause cell damage or are further metabolized and detoxified by glutathione S-transferases (GSTs). This study investigated whether or not the genotypes, CYP2E1, glutathione S-transferase θ (GST T1) and μ (GST M1), correlated the abnormal liver function in vinyl chloride exposed workers. We enrolled 251 workers from 5 polyvinyl chloride plants for this study. The workers who were exposed to VCM were classified into two, high and low exposure groups and the degree of exposure was determined based on their job titles and airborne VCM concentration. The enzyme activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were used as the parameters of liver function. The genotypes, CYP2E1, GST T1 and GST M1, were determined by performing PCR and RFLP on peripheral white blood cell DNA, Other potential risk factors were also ascertained and the confounding effect was adjusted accordingly. Stratified analyses were used to explore the correlation between the alteration of liver function and the genotypes, CYP2E1, GST T1 and GST M1, among the workers exposed to different levels of VCM. The results obtained showed: (1)at low VCM exposure, the odds ratio (OR) of GST T1 non-null genotype on abnormal ALT was 3.8 (95% CI=1.2-14.5) but the CYP2E1 genotype was not associated with abnormal ALT; (2)at high VCM exposure, on the other band, a c2c2 CYP2E1 genotype was associated with increased OR on abnormal ALT (OR=4.8, 95% CI=0.6-34.8) but the GST T1 non-null genotype was not associated with abnormal ALT (OR=0.9, 95% CI=0.2-3,8); and (3)multiple logistic regression also showed strong interactions of the VCM exposure to CYP2E1 as well as to the GST T1 genotype. Thus, These observations suggest that the two genotypes, CYP2E1 and GST T1, may play important roles in the biotransformation of VCM, whose effect leads to liver damage.
延伸閱讀
- 陳香郿（2007）。人類有機陰離子運輸器OATP1B1基因型與抗結核藥物治療期間肝損傷之關聯研究〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://doi.org/10.6831/TMU.2007.00021
- Huang, C. J. (2013). 克雷白氏肺炎桿菌CG43磷酸二酯酶YjcC與二級訊息分子c-di-GMP在壓力反應調控之功能性研究 [doctoral dissertation, National Chiao Tung University]. Airiti Library. https://doi.org/10.6842/NCTU.2013.00403
- 劉宇真（2000）。染料廠員工細胞色素酵素基因型1A2、N-乙醯基轉移酵素基因型第I型與泌尿上皮細胞週期指標之相關研究〔碩士論文，臺北醫學大學〕。華藝線上圖書館。https://www.airitilibrary.com/Article/Detail?DocID=U0007-1704200714342337
- Chen, Z. J. (2013). Mechanism of flippase Drs2p in modulating GTP hydrolysis of Arl1p [master's thesis, National Taiwan University]. Airiti Library. https://doi.org/10.6342/NTU.2013.10510
- Liu, S. S. (2007). Defect reduction and environment stress quality test (ESQT) on GaN p-i-n UV sensor n [doctoral dissertation, National Central University]. Airiti Library. https://www.airitilibrary.com/Article/Detail?DocID=U0031-0207200917343759