The association between a genetic polymorphism of coproporphyrinogen oxidase, dental mercury exposure and neurobehavioral response in humans
The association between a genetic polymorphism of coproporphyrinogen oxidase, dental mercury exposure and neurobehavioral response in humans
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DOI：
10.1016/j.ntt.2005.10.006
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发表时间：
2006-01-01
影响因子：
2.9
通讯作者：
Garabedian, CE
中科院分区：
文献类型：
--
作者：
Echeverria, D;Woods, JS;Garabedian, CE
我们之前描述了编码血红素生物合成途径酶粪卟啉原氧化酶 (CPOX4) 的基因的外显子 4 中的多态性，该多态性显着改变了汞暴露对人类尿卟啉排泄的影响。在这里，我们研究了这种多态性（“CPOX4”）对人类受试者已知受元素汞（Hg 度）暴露影响的神经行为领域、症状和情绪的潜在影响。在尿液和口腔细胞采集当天，对 194 名男性牙医 (DD) 和 233 名女性牙医助理 (DA) 进行了行为测试，他们在职业上接触汞的时间平均分别为 19 和 10 年。受试者没有健康疾病史，并且在牙科行业工作了至少 5 年。 DD 和 DA 中的平均尿汞 (HgU) 水平分别为 3.32 (4.87) 微克/升和 1.98 (2.29) 微克/升。相应的慢性职业汞暴露程度指数（按历史暴露加权）分别为 27.1 (20.6) 和 15.2 (12.3)。 DD 的纯合子常见 (A/A)、杂合子 (A/C) 和纯合多态性 (C/C) 基因型的频率分别为 75%、23% 和 2%，DA 的频率分别为 73%、25% 和 2%。 DD 和 DA 分别进行评估。对年龄、病前智力、饮酒量和教育程度进行控制的回归分析。在 DD 中的九项测量中发现与 HgU (p < 0.05) 的统计显着相关性（BEES 数字跨度（向前和向后）和 WMS-R 视觉再现（N）（正确）、BEES 符号数字（速率）、BEES 手指敲击（Dom/Non-dom）（和交替部分）、手））稳定性（因子 1）和 BEES 跟踪），以及 DA 中的八个度量（BEES 数字跨度（向前）、BEES 符号数字（速率）、BEES 模式辨别（速率）、BEES Trailmaking B、BEES 手指敲击（Dom/Non-dom 和交替）（部分）、手稳定性（因子 1）和振动灵敏度（点击））。 CPOX4 状态与 DD 中的四个测量值（BEES 空间跨度（向前）、BEES 模式记忆（N）（正确）、BEES 符号数字（速率）和 BEES 警惕（命中））和 DA 中的五个测量值（BEES 数字跨度（向前）、WMS-R 视觉再现（N）（正确）、BEES 符号数字（速率）、BEES 简单和选择反应时间（移动））相关。两组均经历了 HgU 和 CPOX4 多态性对数字（速率）的累加效应（无相互作用），而 DAS 对 BEES 数字跨度（向前）和 Beck 的抑郁因子“无价值”也有累加效应。这些探索性发现表明，CPOX4 多态性可能会影响人类受试者与汞暴露相关的特定神经行为功能的易感性 (c) 2005 Elsevier。公司保留所有权利。
We previously described a polymorphism in exon 4 of the gene encoding the heme biosynthetic pathway enzyme, coproporphyrinogen oxidase (CPOX4), which significantly modifies the effect of mercury exposure on urmary porphyrin excretion in humans. Here, we examined potential consequences of this polymorphism ("CPOX4") on performance within neurobehavioral domains, symptoms, and mood that are known to be affected by elemental mercury (Hg degrees) exposure in human subjects. A behavioral test battery was administered on the day of urine and buccal cell collections for 194 male dentists (DDs) and 233 female dental assistants (DAs) occupationally exposed to Hg degrees for an average of 19 and 10 years, respectively. Subjects had no history of health disorders and were employed for a minimum of 5 years in the dental profession. Respective mean urinary mercury (HgU) levels in DDs and DAs were 3.32 (4.87) mu g/l and 1.98 (2.29) mu g/l. Corresponding indices of chronic occupational Hg degrees exposure, weighted for historical exposure, were 27.1 (20.6) and 15.2 (12.3). The frequencies of the bomogygous common (A/A), heterozygous (A/C), and homozygous polymorpbic (C/C) genotypes were 75%, 23% and 2% for DDs and 73%, 25%, and 2% for DAs, respectively. DDs and DAs were evaluated separately. Regression analyses controlled for age, premorbid intelligence, alcohol consumption, and education.Statistically significant associations with HgU (p < 0.05) were found for nine measures among DDs (BEES Digit Span(forward and backward), and WMS-R Visual Reproduction(N) (Correct), BEES Symbol Digit(Rate), BEES Finger Tapping(Dom/Non-dom) (and Alternate Partialed), Hand Steadiness(Factor1), and BEES Tracking), and eight measures among DAs (BEES Digit Span(forward), BEES Symbol Digit(Rate), BEES Pattern Discrimination (Rate), BEES Trailmaking B, BEES Finger Tapping(Dom/Non-dom, and Alternate) (Partialed), Hand Steadiness(Factor1), and Vibration Sensitivity(Hits)). CPOX4 status was associated with four measures in DDs (BEES Spatial Span(Foward), BEES Pattern Memory(N) (Correct), BEES Symbol Digit(Rate), and BEES Vigilance(Hit)) and five measures in DAs (BEES Digit Span(Forward), WMS-R Visual Reproduction(N) (Correct), BEES Symbol Digit(Rate), BEES Simple and Choice Reaction Time(Move). Both groups experienced an additive effect (no interaction tenn) for HgU and the CPOX4 polymorphisms on the Digit(Rate) whereas DAS also had additive effects for BEES Digit Span(Forward) and for Beck's Depression factor 'Worthlessness'. These exploratory findings suggest that the CPOX4 polymorphism may affect susceptibility for specific neurobebavioral functions associated with mercury exposure in human subjects. (c) 2005 Elsevier Inc. All rights reserved.