Association between hemochromatosis genotype and lead exposure among elderly men: the normative aging study.

Abstract

Because body iron burden is inversely associated with lead absorption, genes associated with hemochromatosis may modify body lead burden. Our objective was to determine whether the C282Y and/or H63D hemochromatosis gene (HFE) is associated with body lead burden. Patella and tibia lead levels were measured by K X-ray fluorescence in subjects from the Normative Aging Study. DNA samples were genotyped for C282Y and H63D using polymerase chain reaction/restriction fragment length polymorphism (PCR/RFLP). A series of multivariate linear regression models were constructed with bone or blood lead as dependent variables; age, smoking, and education as independent variables; and C282Y or H63D as independent risk factors and/or effect modifiers. Of 730 subjects, 94 (13%) carried the C282Y variant and 183 (25%) carried the H63D variant. In the crude analysis, mean tibia, patella, and blood lead levels were consistently lower in carriers of either HFE variant compared with levels in subjects with wild-type genotypes. In multivariate analyses that adjusted for age, smoking, and education, having an HFE variant allele was an independent predictor of significantly lower patella lead levels (p < 0.05). These data suggest that HFE variants have altered kinetics of lead accumulation after exposure. Among elderly men, subjects with HFE variants had lower patella lead levels. These effects may be mediated by alterations in lead toxicokinetics via iron metabolic pathways regulated by the HFE gene product and body iron stores.

HFE Genotype, Particulate Air Pollution, and Heart Rate Variability

“…The present findings are consistent with our previous report that HFE variants were associated with lower levels of blood lead and bone lead in the same NAS cohort. 18 The proposed mechanism for this effect was that HFE variants indirectly reduce lead exposure. Subjects with HFE variants are at lower risk for iron deficiency, 33,34 and the overall increase in body iron stores among people with HFE variants may result in reduced expression of proteins that regulate divalent metal absorption, thus reducing the body burden of lead.…”

“…14,15 Because iron stores are inversely associated with the gastrointestinal absorption of multiple potentially toxic metals (lead, cadmium, manganese, copper, and cobalt), 16,17 HFE variants may modify the effect of particulate transition metals, and in previous studies, HFE variants were associated with lower blood and bone levels of lead, a toxic divalent metal. 18 We hypothesized that the HFE genetic polymorphism modifies the effect of ambient PM 2.5 on cardiac autonomic function. We previously found a significant association between PM 2.5 and decreased heart rate variability (HRV), a marker of cardiac autonomic dysfunction and a predictor of sudden cardiac death and arrhythmia, 19,20 among older men.…”

Characterizing Golden Eagle Risk to Lead and Anticoagulant Rodenticide Exposure: A Review

“…The gene codes for a protein designated HFE and has two variants: C282Y and H63D. Wright et al (2004) studied 730 men from the Normative Aging Study and found that the presence of a hemochromatosis variant, either C282Y or H63D, predicted lower bone and blood lead concentration. Based on the fact that iron…”

“…status is inversely related to lead absorption, Wright et al (2004) hypothesized that the results may be secondary to increased iron stores among HFE variant carriers leading to decreased lead absorption in the gastrointestinal tract. Previously, Barton et al (1994) found that homozygous individuals who suffered from hemochromatosis had higher PbB than individuals who did not have the gene.…”

“…An additional study found no difference in PbB between subjects with hemochromatosis and controls (Åkesson et al 2000). Wright et al (2004) speculated that the different results could be due to the different characteristics of the participants studied in terms of age, health status, and sex.…”