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Genes may modify risk of lead poisoning
By Bijal P. Trivedi

Scientists at Johns Hopkins University, in Baltimore, Maryland, are finding that susceptibility to lead poisoning varies widely, and have identified variations in two genes that influence how lead is absorbed, where it is stored, and how it is eliminated from the body.

Variants of the ALAD (delta-aminolevulinic acid dehydratase enzyme) gene, ALAD1 and ALAD2, and variants of the VDR (vitamin D receptor) gene, VDR B and VDR b, influence lead levels in Korean lead workers, according to a report published in a recent issue of Environmental Health Perspectives.

The researchers determined the variants of ALAD and VDR carried by each of the 798 Korean lead workers and 135 control workers and looked for associations between blood, bone and urine lead levels.

In contrast to ALAD1, ALAD2 was associated with higher blood lead levels, which confirmed previous findings. Compared to VDR b, VDR B could be tied to higher lead levels in the blood, bone and urine, which is a new observation, says Brian Schwartz, of the Johns Hopkins School of Hygiene and Public Health, who led the study.

The ALAD enzyme manufactures part of the hemoglobin protein and is found in red blood cells. When lead comes in contact with ALAD it binds to it tightly, inhibiting the enzyme. Schwartz speculates that ALAD2, which binds lead more tightly than ALAD1, may confer protection by sequestering lead in the blood and preventing deposition in organs and nerves.

VDR, which is known to influence bone density, is thought to increase bone lead due to greater uptake of lead in the intestine via the VDR B variant.

An unusual finding uncovered by the Hopkins researchers was that a higher proportion of the Korean lead workers carried VDR B and ALAD2 gene variants compared to the control workers.

"It is possible that we are seeing more of these variants because lead workers carrying ALAD1 and or two copies of the VDR b variant are more susceptible to the effects of lead exposure and actually leave the factory due to symptoms. Maybe VDR B and ALAD2 confer some protection from lead poisoning and workers with these, remain at the factories—but this is all speculative," says Schwartz. "We need further studies to confirm the results."

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Schwartz, B.S. et al. Associations of blood lead, dimercaptosuccinic acid-chelatable lead, and tibia lead with polymorphisms in the vitamin D receptor and [delta]-aminolevulinic acid dehydratase genes. Environ Health Perspect 108, 949-954 (October 2000).

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