Genetic susceptibility to lead poisoning

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 certa in individuals more vulnerable to environmental toxins such as lead. At lea st three polymorphic genes have been identified that potentially can influe nce the bioaccumulation and toxicokinetics of lead in humans. The first gen e to be discussed in this review is the gene coding for delta-aminolevulini c acid dehydratase (ALAD), an enzyme of heme biosynthesis, that exists in t wo polymorphic forms. The resulting isozymes have been shown to affect the blood and bone lead levels in human populations. The effects of ALAD in lea d 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 t he gut and into calcium-rich tissues such as bone. Recent findings suggest that VDR polymorphism may influence the accumulation of lead in bone. Final ly, the third gene to be discussed here that may influence the absorption o f lead is the hemochromatosis gene coding for the HFE protein. The presence of mutations in the HFE gene leads to hemochromatosis in homozygotic indiv iduals. Because of the associations between iron and lead transport, it is possible that polymorphisms in the HFE gene may also influence the absorpti on of lead, but this has not yet been studied. More studies will be needed to define the role of these genes in lead intoxication.