Pb Affects BP.

Closing In on Contributing Factors

Among the negative health effects of lead absorption are demonstrated increases in blood pressure and the risk of developing chronic high blood pressure, or hypertension. In this issue, a collaboration between Korean and American researchers provides a more detailed picture of this relationship as well as new evidence that variations in the gene for the vitamin D receptor (VDR), which is known to modify the toxicokinetics of lead, influence blood pressure [EHP 109:383-389].

Byung-Kook Lee of Soonchunhyang University in Korea, Brian S. Schwartz of the Johns Hopkins School of Hygiene and Public Health, and their colleagues examined Korean workers who worked at facilities where lead was used. The researchers assessed lead absorption in the workers by measuring lead in blood, the tibia, and soft tissues. They then correlated these concentrations with measures of blood pressure and hypertension. In addition, they looked at the influence of two obvious gene candidates, those for the VDR and those for the enzyme [Delta]-aminolevulinic acid dehydratase (ALAD). Both genes have been shown to modify the toxicokinetics of lead--that is, its absorption, distribution, metabolism, and excretion. For example, ALAD genotype is known to influence blood lead concentrations, and VDR genotype is known to influence lead concentrations in blood, bone, and soft tissues. Each gene is also polymorphic, meaning that several variants (polymorphisms) of the gene exist in a population. Possession of a particular polymorphism could alter the way a person's body responds to absorbed lead.

The researchers explored this relationship in 798 lead workers and 135 control subjects. For all three measures of lead, higher concentrations were associated with higher systolic blood pressure. There were no associations between the lead biomarkers and diastolic blood pressure, but bone lead was a predictor of hypertension status. This last finding is particularly important, say the authors, because it suggests that lead has a chronic, cumulative influence on hypertension risk.

An entirely new finding was that variations in VDR genotype affected all of the blood pressure measures. Lee and colleagues examined the BsmI polymorphism of the VDR, which has three genotypes--bb, Bb, and BB. Workers who carried the B allele of the BsmI polymorphism (in either the BB or Bb combination) had higher systolic blood pressure, diastolic blood pressure, and prevalence of hypertension than did workers who did not carry the B gene allele (that is, those with the bb combination). In fact, the risk of hypertension was doubled among subjects with the VDR B allele. The researchers also found that the B variant modified the effects of age on systolic blood pressure: workers with the BB or Bb genotype had greater increases in blood pressure with increasing age. By contrast, variations in the ALAD gene produced no noticeable differences in blood pressure measures.

The authors suggest that if lead influences blood pressure by directly interacting with the proteins coded for by the VDR gene, the different genotypes would have produced different effects on the measured relationships between lead concentrations and blood pressure. Since this was not the case, it is likely that lead and VDR genotype each have an independent influence on blood pressure. Exactly how variations in the VDR gene affect blood pressure is not clear, but the authors point out that the VDR plays a critical role in intestinal calcium regulation and that there is a demonstrated interrelationship between calcium, lead, and blood pressure. One possibility is that the VDR could influence the absorption of calcium and lead from the gastrointestinal tract or the release of calcium and lead from bones.