Apolipoprotein E genotyping as a potential biomarker for mercury neurotoxicity
Apolipoprotein E genotyping as a potential biomarker for mercury neurotoxicity
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DOI：
10.3233/jad-2003-5303
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发表时间：
2003-01-01
影响因子：
4
通讯作者：
Krone, Cheryl A.
中科院分区：
文献类型：
--
作者：
Godfrey, Michael E.;Wojcik, Damian P.;Krone, Cheryl A.
载脂蛋白-E（apo-E）基因分型已被研究作为重金属易感性的指标（即，铅）神经毒性。此外，apo-E ε（ε）4等位基因是神经退行性疾病（包括阿尔茨海默病（AD））的主要风险因素。本文讨论了这一危险因素的理论生化基础，400例假定汞相关的神经精神症状和载脂蛋白E测定的患者的数据支持。在患者中发现了向高风险apo-E β 4组的统计学相关变化（p < 0.001）。患者平均有13.7个牙科汞合金填充物和31.5个汞合金表面。这远远超过了汞合金中汞的最大可耐受日摄入量，由于症状和体征的非特异性，慢性低水平汞中毒的临床诊断和证据一直很困难。牙科汞合金是一般人群中汞的最大来源，大脑、血液和尿液中的汞含量随着汞合金数量和口腔中汞合金表面的数量而相应增加。汞的升高的身体负担的确认，可以通过测量尿汞，激发后，与2，3，-二巯基丙磺酸盐（DMPS），这是在150 patients.Apo-E基因分型值得调查作为一个临床有用的生物标志物的神经病理学，包括AD，当受到长期汞暴露的风险增加。此外，当临床发现表明慢性汞暴露的不良影响时，DMPS尿汞挑战似乎是一种简单、廉价的程序，可提供客观的确证性证据。现在，初级保健从业人员有机会帮助确定那些风险更大的人，并可能预防随后的神经系统恶化。
Apolipoprotein-E (apo-E) genotyping has been investigated as an indicator of susceptibility to heavy metal (i.e., lead) neurotoxicity. Moreover, the apo-E epsilon (epsilon)4 allele is a major risk factor for neurodegenerative conditions, including Alzheimer's disease (AD). A theoretical biochemical basis for this risk factor is discussed herein, supported by data from 400 patients with presumptive mercury-related neuro-psychiatric symptoms and in whom apo-E determinations were made. A statistically relevant shift toward the at-risk apo-E epsilon 4 groups was found in the patients (p < 0.001). The patients possessed a mean of 13.7 dental amalgam fillings and 31.5 amalgam surfaces. This far exceeds the number capable of producing the maximum identified tolerable daily intake of mercury from amalgam.The clinical diagnosis and proof of chronic low-level mercury toxicity has been difficult due to the non-specific nature of the symptoms and signs. Dental amalgam is the greatest source of mercury in the general population and brain, blood and urine mercury levels increase correspondingly with the number of amalgams and amalgam surfaces in the mouth. Confirmation of an elevated body burden of mercury can be made by measuring urinary mercury, after provocation with 2,3,-dimercapto-propane sulfonate (DMPS) and this was measured in 150 patients.Apo-E genotyping warrants investigation as a clinically useful biomarker for those at increased risk of neuropathology, including AD, when subjected to long-term mercury exposures. Additionally, when clinical findings suggest adverse effects of chronic mercury exposure, a DMPS urine mercury challenge appears to be a simple, inexpensive procedure that provides objective confirmatory evidence. An opportunity could now exist for primary health practitioners to help identify those at greater risk and possibly forestall subsequent neurological deterioration.