Evidence of genetic effects on blood lead concentration

Abstract

Background: Lead is an environmental pollutant that causes acute and chronic toxicity. Surveys have related mean blood lead concentrations to exogenous sources, including industrial activity, use of lead-based paints, or traffic density. However, there has been little investigation of individual differences in lead absorption, distribution, or toxicity, or of genetic causes of such variation.

Objectives: We assessed the genetic contribution to variation in blood lead concentration in adults and conducted a preliminary search for genes producing such variation.

Methods: Erythrocyte lead concentration was measured by inductively coupled plasma mass spectrometry in venous blood samples from 2,926 Australian adult male and female twins. Mean lead concentrations were compared by place of residence, social class and education, and by the subjects' age, sex, alcohol intake, smoking habits, iron status, and HFE genotype.

Results: After adjustment for these covariates, there was strong evidence of genetic effects but not for shared environmental effects persisting into adult life. Linkage analysis showed suggestive evidence (logarithm of odds = 2.63, genome-wide p = 0.170) for a quantitative trait locus affecting blood lead values on chromosome 3 with the linkage peak close to SLC4A7, a gene whose product affects lead transport.

Conclusions: We conclude that genetic variation plays a significant role in determining lead absorption, lead distribution within the body, or both.

Figure 1

Results of linkage analysis for erythrocyte lead (residuals after adjusting for covariates). Each panel represents one chromosome; the x-axis shows genetic distance from the p-terminal end, and centromeres are indicated by filled triangles below this axis. The y-axis shows LOD scores, and the lines at 3.0 and 1.6 on the γ-axis represent the empirical “significant” and “suggestive” values for genome-wide significance as determined by simulation.

Figure 2

Linkage results for chromosome 3. The x-axis shows genetic distance from the p-terminal end and the y-axis shows LOD scores, and the lines at 3.0 and 1.6 on the y-axis represent the empirical “significant” and “suggestive” values for genome-wide significance as determined by simulation. Arrow indicates the position of SLC4A7.