细胞色素P-450 MspI基因多态性对焦炉工人血清肝功能指标的调节作用

Modulating influence of cytochrome P-450 MspI polymorphism on serum liver function profiles in coke oven workers.

作者信息

Wu M T, Ho C K, Huang S L, Yeh Y F, Liu C L, Mao I F, Christiani D C

机构信息

Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.

出版信息

Occup Environ Med. 1999 Mar;56(3):159-63. doi: 10.1136/oem.56.3.159.

DOI:10.1136/oem.56.3.159

PMID:10448323

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1757713/

Abstract

OBJECTIVES

It was reported previously that topside oven workers with heavy exposure to coke oven emissions had increased serum activities of hepatic aminotransferase in one coke oven plant. This study was conducted to investigate the modifying effect of CYP1A1 MspI polymorphism on liver function profiles in coke oven workers.

METHODS

88 coke oven workers from a large steel company in Taiwan were studied in 1995-6. Exposure was categorised by work area: topside oven workers and sideoven workers. Liver function profiles including serum aspartate aminotransferase (AST), alanine aminotransferase (ALT), r-glutamyl transpeptidase (GGT), alkaline phosphatase (ALP), and total bilirubin (BIL) were examined in the morning after personal exposure measurements. The MspI polymorphism was determined by polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP).

RESULTS

Five of 23 (22%) topside oven workers and seven of 65 (11%) sideoven workers had the CYP1A1 MspI homozygous variant genotype. With sideoven workers with the combined wild type and heterozygous variant as the reference group in multiple regression models, it was found that topside oven workers with the combined traits had mean AST and ALT activities that were 21% and 46% higher (95% confidence interval (95% CI) 4% to 42% and 12% to 91%, respectively) than the reference group after adjusting for appropriate confounders. Also, topside oven workers with the homozygous variant trait had mean AST, ALT, and GGT activities that were 59%, 68%, and 157% higher (95% CI 21% to 109%, 6% to 168%, and 39% to 374%, respectively) than the reference group. The prevalence of an abnormal hepatocellular pattern (AST > 37 IU/l or ALT > 39 IU/l) was more common in the topside oven workers with the homozygous variant than in the sideoven workers with the other combined genotypes (adjusted odds ratio 9.9, 95% CI 1.2 to 82.3) after adjusting for appropriate confounders.

CONCLUSIONS

The CYP1A1 MspI polymorphism may modify the biotransformation of coke oven emissions, which results in hepatocellular damage in coke oven workers.

摘要

目的

此前有报道称，在一家炼焦厂中，重度接触焦炉排放物的炉顶工人血清肝转氨酶活性升高。本研究旨在调查CYP1A1 MspI基因多态性对焦炉工人肝功能指标的修饰作用。

方法

1995 - 1996年对台湾一家大型钢铁公司的88名焦炉工人进行了研究。根据工作区域对接触情况进行分类：炉顶工人和炉侧工人。在个人接触测量后的早晨，检测肝功能指标，包括血清天冬氨酸转氨酶（AST）、丙氨酸转氨酶（ALT）、γ-谷氨酰转肽酶（GGT）、碱性磷酸酶（ALP）和总胆红素（BIL）。通过聚合酶链反应（PCR）和限制性片段长度多态性（RFLP）确定MspI基因多态性。

结果

23名炉顶工人中有5名（22%）以及65名炉侧工人中有7名（11%）具有CYP1A1 MspI纯合变异基因型。在多元回归模型中，以炉侧工人中野生型和杂合变异型组合为参照组，发现经适当混杂因素校正后，具有两种性状组合的炉顶工人的AST和ALT平均活性分别比参照组高21%和46%（95%置信区间（95%CI）分别为4%至42%和12%至91%）。此外，具有纯合变异性状的炉顶工人的AST、ALT和GGT平均活性分别比参照组高59%、68%和157%（95%CI分别为21%至109%、6%至168%和39%至374%）。在经适当混杂因素校正后，具有纯合变异的炉顶工人中肝细胞异常模式（AST>37 IU/L或ALT>39 IU/L）的患病率比具有其他组合基因型的炉侧工人更常见（校正比值比9.9，95%CI为1.2至82.3）。