Blood lead is associated with elevated blood pressure in several studies of the general population and occupational groups although the mechanism of action is unknown. Lead inhibits the membrane protein, sodium-potassium adenosine triphosphatase (Na+-K+ ATPase) in lead-exposed animals and in in vitro studies. This enzyme, which may have a role in blood pressure regulation, maintains intracellular sodium and potassium concentrations and the electrochemical gradient across the membrane. Genetic differences in Na+-K+ ATPase could explain some of the variation in the strength of the relation between blood pressure and blood lead in previous studies. In 1996 - 1997, the authors studied the association of blood pressure, hypertension prevalence, and polymorphisms in the gene for the alpha two subunit of Na+-K+ ATPase (ATP1A2) in 220 former organolead manufacturing workers from New Jersey. Subjects were genotyped for a restriction fragment length polymorphism (RFLP) on the ATP1A2 gene. The association between blood lead and blood pressure was stronger among individuals homozygous for the variant allele. Genotype also was associated with hypertension (adjusted odds ratio [95 percent confidence interval], 7.7 [1.9 - 31.4]). Finally, the variant allele was 1.8 times more common among African Americans than among Caucasians. The RFLP may indicate susceptibility to the effect of lead on blood pressure. Moreover, the alpha two subunit gene (or a closely linked gene) may be involved in the pathophysiology of hypertension. However, due to the small number with the susceptible genotype these conclusions should be considered preliminary until they can be replicated.
Learning Objectives: 1. To understand the use of genetic polymorphisms to study gene-environment interactions
Keywords: Lead, Chronic (CVD)
Presenting author's disclosure statement:
Organization/institution whose products or services will be discussed: None
I do not have any significant financial interest/arrangement or affiliation with any organization/institution whose products or services are being discussed in this session.