Genetic susceptibility to lead poisoning.
Genetic susceptibility to lead poisoning.
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DOI：
10.1289/ehp.00108s123
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发表时间：
2000-03
影响因子：
10.4
通讯作者：
中科院分区：
文献类型：
--
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在调节一般人群中的铅中毒方面已经取得了重大进展，但使用环境毒物易感性遗传标记的研究提出了一个问题，即基因是否会使某些人更容易受到铅等环境毒素的影响。至少有三个多态性基因已被确定，可能会影响铅在人体内的生物积累和毒理学。在这篇综述中要讨论的第一个基因是编码δ-氨基乙酰丙酸脱氢酶（ALAD）的基因，ALAD是血红素生物合成的酶，以两种多态形式存在。由此产生的同工酶已被证明会影响人类血液和骨铅水平。ALAD在铅中毒中的作用也在实验室小鼠中进行了研究，这些小鼠对这种酶的遗传剂量不同。第二个基因是维生素D受体（VDR）基因。VDR参与钙通过肠道吸收并进入富含钙的组织如骨骼。最近的研究表明，VDR基因多态性可能会影响铅在骨中的积累。最后，这里要讨论的第三个可能影响铅吸收的基因是编码HFE蛋白的血色素沉着症基因。HFE基因突变的存在导致纯合子个体的血色沉着病。由于铁和铅转运之间的关联，HFE基因的多态性也可能影响铅的吸收，但这还没有被研究。需要更多的研究来确定这些基因在铅中毒中的作用。
Major strides have been taken in the regulation of lead intoxication in the general population, but studies using genetic markers of susceptibility to environmental toxicants raise the question of whether genes can make certain individuals more vulnerable to environmental toxins such as lead. At least three polymorphic genes have been identified that potentially can influence the bioaccumulation and toxicokinetics of lead in humans. The first gene to be discussed in this review is the gene coding for delta-aminolevulinic acid dehydratase (ALAD), an enzyme of heme biosynthesis, that exists in two polymorphic forms. The resulting isozymes have been shown to affect the blood and bone lead levels in human populations. The effects of ALAD in lead intoxication have also been studied in laboratory mice that differ in the genetic dose for this enzyme. The second gene reviewed here is the vitamin D receptor (VDR) gene. The VDR is involved in calcium absorption through the gut and into calcium-rich tissues such as bone. Recent findings suggest that VDR polymorphism may influence the accumulation of lead in bone. Finally, the third gene to be discussed here that may influence the absorption of lead is the hemochromatosis gene coding for the HFE protein. The presence of mutations in the HFE gene leads to hemochromatosis in homozygotic individuals. Because of the associations between iron and lead transport, it is possible that polymorphisms in the HFE gene may also influence the absorption of lead, but this has not yet been studied. More studies will be needed to define the role of these genes in lead intoxication.