Format

Send to

Choose Destination
See comment in PubMed Commons below
Environ Health Perspect. 2008 Sep;116(9):1261-6. doi: 10.1289/ehp.11233.

Variants in iron metabolism genes predict higher blood lead levels in young children.

Author information

  • 1Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts, USA.

Abstract

BACKGROUND:

Given the association between iron deficiency and lead absorption, we hypothesized that variants in iron metabolism genes would predict higher blood lead levels in young children.

OBJECTIVE:

We examined the association between common missense variants in the hemochromatosis (HFE) and transferrin (TF) genes and blood lead levels in 422 Mexican children.

METHODS:

Archived umbilical cord blood samples were genotyped for HFE (H63D and C282Y) and TF (P570S) variants. Blood lead was measured at 24, 30, 36, 42, and 48 months of age. A total of 341 subjects had at least one follow-up blood lead level available and data available on covariates of interest for inclusion in the longitudinal analyses. We used random-effects models to examine the associations between genotype (HFE, TF, and combined HFE + TF) and repeated measures of blood lead, adjusting for maternal blood lead at delivery and child's concurrent anemia status.

RESULTS:

Of 422 children genotyped, 17.7, 3.3, and 18.9% carried the HFE H63D, HFE C282Y, and TF P570S variants, respectively. One percent of children carried both the HFE C282Y and TF P570S variants, and 3% of children carried both the HFE H63D and TF P570S variants. On average, carriers of either the HFE (beta = 0.11, p = 0.04) or TF (beta = 0.10, p = 0.08) variant had blood lead levels that were 11% and 10% higher, respectively, than wild-type subjects. In models examining the dose effect, subjects carrying both variants (beta = 0.41, p = 0.006) had blood lead 50% higher than wild-type subjects and a significantly higher odds of having a blood lead level > 10 microg/dL (odds ratio = 18.3; 95% confidence interval, 1.9-177.1).

CONCLUSIONS:

Iron metabolism gene variants modify lead metabolism such that HFE variants are associated with increased blood lead levels in young children. The joint presence of variant alleles in the HFE and TF genes showed the greatest effect, suggesting a gene-by-gene-by-environment interaction.

KEYWORDS:

C282Y; H63D; P570S; children; hemochromatosis; iron; lead; polymorphism; transferrin

PMID:
18795173
PMCID:
PMC2535632
DOI:
10.1289/ehp.11233
[PubMed - indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for National Institute of Environmental Health Sciences Icon for PubMed Central
    Loading ...
    Support Center