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儿茶酚-O-甲基转移酶(COMT)VAL158MET功能多态性、牙科汞暴露与自我报告的症状及情绪

Catechol O-methyltransferase (COMT) VAL158MET functional polymorphism, dental mercury exposure, and self-reported symptoms and mood.

作者信息

Heyer Nicholas J, Echeverria Diana, Martin Michael D, Farin Federico M, Woods James S

机构信息

Battelle Centers for Public Health Research and Evaluation, Seattle, WA, USA.

出版信息

J Toxicol Environ Health A. 2009;72(9):599-609. doi: 10.1080/15287390802706405.

Abstract

Associations were evaluated between a functional single nucleotide polymorphism (Val158Met) in the gene encoding the catecholamine catabolic enzyme catechol O-methyltransferase (COMT), dental mercury exposure, and self-reported symptoms and mood among 183 male dentists and 213 female dental assistants. Self-reported symptoms, mood, and detailed work histories were obtained by computerized questionnaire. Spot urine samples were collected and analyzed for mercury concentrations to evaluate recent exposures, whereas a chronic mercury exposure index for all subjects was created from the work histories. COMT polymorphism status was determined using a polymerase chain reaction (PCR)-based assay. Scores for current, recent, and chronic self-reported symptom groups and six self-reported mood factors were evaluated with respect to recent and chronic mercury exposure and COMT polymorphism status. Multiple regression analysis controlled for age, socioeconomic status, tobacco and alcohol use, self-reported health problems, and medications. Separate evaluations were conducted for dentists and dental assistants. No consistent patterns of association between either urinary mercury concentration or the chronic index of mercury exposure and any category of symptoms were observed. However, consistent and significant associations were found between increased symptoms and the COMT polymorphism involving the double allelic substitution (full mutation) compared to subjects with no substitutions. Associations with mood were limited to polymorphism status among female dental assistants, and were observed for four of six mood factors and overall mood score. These findings extend evidence of genetic factors potentially affecting human susceptibility to the toxic effects of mercury and other environmental chemicals.

摘要

在183名男性牙医和213名女性牙科助理中,对儿茶酚胺分解代谢酶儿茶酚-O-甲基转移酶(COMT)编码基因中的功能性单核苷酸多态性(Val158Met)、牙科汞暴露与自我报告的症状及情绪之间的关联进行了评估。通过计算机化问卷获取自我报告的症状、情绪及详细工作史。收集即时尿样并分析汞浓度以评估近期暴露情况,同时根据工作史为所有受试者创建慢性汞暴露指数。使用基于聚合酶链反应(PCR)的检测方法确定COMT多态性状态。针对近期和慢性汞暴露以及COMT多态性状态,评估当前、近期和慢性自我报告症状组的得分以及六个自我报告情绪因素的得分。多元回归分析对年龄、社会经济地位、烟草和酒精使用、自我报告的健康问题及用药情况进行了控制。分别对牙医和牙科助理进行了评估。未观察到尿汞浓度或慢性汞暴露指数与任何症状类别之间存在一致的关联模式。然而,与无替换的受试者相比,发现症状增加与涉及双等位基因替换(完全突变)的COMT多态性之间存在一致且显著的关联。与情绪的关联仅限于女性牙科助理的多态性状态,在六个情绪因素中的四个以及总体情绪得分方面均有观察到。这些发现扩展了遗传因素可能影响人类对汞及其他环境化学物质毒性作用易感性的证据。

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