Dataset Information

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

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

SUBMITTER: Hopkins MR

PROVIDER: S-EPMC2535632 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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

Hopkins Marianne R MR Ettinger Adrienne S AS Hernández-Avila Mauricio M Schwartz Joel J Téllez-Rojo Martha María MM Lamadrid-Figueroa Héctor H Bellinger David D Hu Howard H Wright Robert O RO

Environmental health perspectives 20080901 9

<h4>Background</h4>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.<h4>Objective</h4>We examined the association between common missense variants in the hemochromatosis (HFE) and transferrin (TF) genes and blood lead levels in 422 Mexican children.<h4>Methods</h4>Archived umbilical cord blood samples were genotyped for HFE (H63D and C282Y) and TF (P570S) variants. Bl ...[more]

PMID: 18795173

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Project description:Background:Lead can cause significant biological and neurologic damage, even at small concentrations, and young children are at higher risk. Informal recycling of lead batteries and lead-based workshops/industries have increased the burden of lead toxicity in developing countries, including India. Many informal recycling lead battery workshops have been established by the local people of Patna, Bihar as self-employment opportunities. However, most of the residents are not aware of the risk factors associated with lead poisoning. Objectives:The present pilot study aimed to assess blood lead levels (BLLs) and hemoglobin levels among children aged between 3 to 12 years in the settlement of Karmalichak near Patna, India. Materials and Methods:Children residing near the informal lead battery manufacturing unit were selected for BLL assessment. A total of 41 children were enrolled in the questionnairebased survey. Results:All the children in the present study had detectable lead concentrations in their blood. Only 9% of the studied children had a BLL ?5 ?g/dl, while 91% children had a BLL above >5 ?g/dl. Conclusions:The present study carried out in children of Karmalichak region of Patna, India was an attempt to better understand the problem of lead toxicity, describe the epidemiology of its adverse effects, identify sources and routes of exposure, illustrate the clinical effects and develop strategies of prevention so that remedial measures may be taken by government agencies and regulatory bodies. In view of the high lead levels in children in the study area, attempts are being made to develop strategies for future prevention by relocating the informal battery recycling workshops from the area. Moreover, parents have been advised to increase nutritional supplementation of children by providing calcium-, iron- and zinc-rich foods, including milk and vegetables. Participant Consent:Obtained. Ethical Approval:The study was approved by the ethical committee of Era's Lucknow Medical College & Hospital, Era University, Lucknow (India). Competing Interests:The authors declare no competing financial interests.

Project description:BackgroundInjectable contraceptive use is common, with 74 million users worldwide. Use of the injectable contraceptive depot medroxyprogesterone acetate (DMPA) is associated with bone mineral density loss. We hypothesize that increased bone resorption with DMPA use allows for mobilization of the toxic metal lead stored in bone to blood, presenting users with increased systemic exposure to lead.ObjectiveThe objective of our study was to investigate the association between current DMPA use and blood lead concentrations.MethodsWe conducted a cross-sectional analysis using enrollment data from the Study of Environment, Lifestyle & Fibroids (SELF), a cohort of 1,693 African-American women who were 23-35 years of age. Data on DMPA use were collected by computer-assisted telephone interview. Blood lead concentrations were measured in whole blood samples among 1,548 participants (91% of cohort). We estimated the adjusted percent difference in blood lead concentrations and 95% confidence intervals (CI) between current DMPA users and nonusers using multivariable linear regression.ResultsGeometric mean blood lead concentration was 0.69μg/dL (95% CI: 0.67, 0.71). After adjustment, current DMPA users (7% of cohort) had blood lead concentrations that were 18% higher than those of nonusers (95% CI: 8%, 29%). Similar associations were observed with additional analyses to assess for potential bias from smoking, DMPA-induced amenorrhea, use of estrogen-containing contraceptives, having given birth in the prior year, and history of medical conditions or current medication use associated with bone loss.DiscussionOur results indicate that current DMPA use is associated with increased blood lead concentrations. Further research, particularly in populations highly exposed to lead, is warranted to consider tradeoffs between the adverse effects of lead on human health and the importance of DMPA as a contraceptive option to prevent unintended pregnancy. https://doi.org/10.1289/EHP7017.

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

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

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