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慢性低水平汞暴露、脑源性神经营养因子多态性及其与认知和运动功能的关联。

Chronic low-level mercury exposure, BDNF polymorphism, and associations with cognitive and motor function.

作者信息

Echeverria Diana, Woods James S, Heyer Nicholas J, Rohlman Dianne S, Farin Federico M, Bittner Alvah C, Li Tingting, Garabedian Claire

机构信息

Battelle Centers for Public Health Research and Evaluation, Seattle, WA 98109, USA.

出版信息

Neurotoxicol Teratol. 2005 Nov-Dec;27(6):781-96. doi: 10.1016/j.ntt.2005.08.001.

Abstract

Potential cognitive and motor effects from exposure to elemental mercury (Hg(0)) were examined in the presence and absence of a polymorphism (Val66Met) in brain-derived neurotrophic factor (BDNF). A group of 194 male dentists (DDs) and 233 female dental assistants (DAs) were occupationally exposed to mercury and had no history of kidney or nervous system disorders. Acute exposure was measured using spot urinary Hg (HgU) concentrations (average 3.32 and 1.98 microg/l, respectively) and indices of chronic occupational exposure (26.3 and 14.9 years, respectively, weighted for historical exposures). The BDNF status was 68% and 66% wild type, 26% and 30% single substitution, and 5% and 4% full mutation for DDs and DAs, respectively. DDs and DAs were evaluated separately. Regression analyses controlled for age, premorbid intelligence, alcohol consumption, and education. Statistically significant adverse associations with HgU (p<.05) were found for nine measures among DDs (Digit Span (Forward), Digit and Spatial Span(Backward), Visual Reproduction, Finger Tapping(Dominant, Alternate, and Alternate Partialed), Hand Steadiness, and Tracking), and eight measures among DAs (Digit Span(Forward), Visual Reproduction, Pattern Discrimination(Rate), Symbol Digit(Rate), Trailmaking B, Finger Tapping(Dominant and Alternate Partialed), and Hand Steadiness). The BDNF status was associated with four measures in DDs and three measures in DAs. Joint effects were found for Finger Tapping(Alternate and Alternate Partialed) in DDs and Hand Steadiness and Trailmaking B in DAs. Joint effects were additive in all cases. Performance on verbal intelligence and reaction time were not associated with either HgU or BDNF status. A test of threshold effect for the association of Hand Steadiness with HgU demonstrated no lower boundary in both DDs and DAs. No associations were observed with estimates of chronic mercury exposure. Our findings are applicable to exposure levels of the general population and identify a potentially vulnerable group with a BDNF polymorphism.

摘要

在存在和不存在脑源性神经营养因子(BDNF)基因多态性(Val66Met)的情况下,研究了暴露于元素汞(Hg(0))对认知和运动的潜在影响。一组194名男性牙医(DDs)和233名女性牙科助手(DAs)职业性接触汞,且无肾脏或神经系统疾病史。急性暴露通过即时尿汞(HgU)浓度(分别平均为3.32和1.98微克/升)和慢性职业暴露指数(分别为26.3和14.9年,根据既往暴露情况加权)来衡量。BDNF状态方面,DDs中野生型分别为68%和66%,单替换分别为26%和30%,完全突变分别为5%和4%;DAs中野生型分别为68%和66%,单替换分别为26%和30%,完全突变分别为5%和4%。DDs和DAs分别进行评估。回归分析对年龄、病前智力、饮酒量和教育程度进行了控制。在DDs中,发现有9项指标与HgU存在统计学显著的不良关联(p<0.05)(数字广度(顺背)、数字和空间广度(倒背)、视觉再现、手指敲击(优势手、非优势手和非优势手部分)、手部稳定性和追踪);在DAs中,有8项指标与HgU存在统计学显著的不良关联(数字广度(顺背)、视觉再现、图案辨别(速度)、符号数字(速度)、连线测验B、手指敲击(优势手和非优势手部分)和手部稳定性)。BDNF状态与DDs中的4项指标以及DAs中的3项指标相关。在DDs中发现手指敲击(非优势手和非优势手部分)以及在DAs中发现手部稳定性和连线测验B存在联合效应。所有情况下联合效应均为相加性。言语智力和反应时间的表现与HgU或BDNF状态均无关联。对手部稳定性与HgU关联的阈值效应测试表明,DDs和DAs中均无下限。未观察到与慢性汞暴露估计值的关联。我们的研究结果适用于一般人群的暴露水平,并确定了一个具有BDNF基因多态性的潜在易感群体。

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