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Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study
BACKGROUND: Given the relationship between iron metabolism and lead toxicokinetics, we hypothesized that polymorphisms in iron metabolism genes might modify maternal-fetal lead transfer. The objective of this study was to determine whether maternal and/or infant transferrin (TF) and hemochromatosis...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271345/ https://www.ncbi.nlm.nih.gov/pubmed/25287020 http://dx.doi.org/10.1186/1476-069X-13-77 |
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author | Karwowski, Mateusz P Just, Allan C Bellinger, David C Jim, Rebecca Hatley, Earl L Ettinger, Adrienne S Hu, Howard Wright, Robert O |
author_facet | Karwowski, Mateusz P Just, Allan C Bellinger, David C Jim, Rebecca Hatley, Earl L Ettinger, Adrienne S Hu, Howard Wright, Robert O |
author_sort | Karwowski, Mateusz P |
collection | PubMed |
description | BACKGROUND: Given the relationship between iron metabolism and lead toxicokinetics, we hypothesized that polymorphisms in iron metabolism genes might modify maternal-fetal lead transfer. The objective of this study was to determine whether maternal and/or infant transferrin (TF) and hemochromatosis (HFE) gene missense variants modify the association between maternal blood lead (MBL) and umbilical cord blood lead (UCBL). METHODS: We studied 476 mother-infant pairs whose archived blood specimens were genotyped for TF P570S, HFE H63D and HFE C282Y. MBL and UCBL were collected within 12 hours of delivery. Linear regression models were used to examine the association between log-transformed MBL and UCBL, examine for confounding and collinearity, and explore gene-environment interactions. RESULTS: The geometric mean MBL was 0.61 μg/dL (range 0.03, 3.2) and UCBL 0.42 (<0.02, 3.9). Gene variants were common with carrier frequencies ranging from 12-31%; all were in Hardy-Weinberg equilibrium. In an adjusted linear regression model, log MBL was associated with log UCBL (β = 0.92, 95% CI: 0.82, 1.03; p < 0.01) such that a 1% increase in MBL was associated with a 0.92% increase in UCBL among infants born to wild-type mothers. In infants born to C282Y variants, however, a 1% increase in MBL is predicted to increase UCBL 0.65% (β(Main Effect) = −0.002, 95% CI: −0.09, −0.09; p = 0.97; β(Interaction) = −0.27, 95% CI: −0.52, −0.01; p = 0.04), representing a 35% lower placental lead transfer among women with MBL 5 μg/dL. CONCLUSIONS: Maternal HFE C282Y gene variant status is associated with greater reductions in placental transfer of lead as MBL increases. The inclusion of gene-environment interaction in risk assessment models may improve efforts to safeguard vulnerable populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1476-069X-13-77) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4271345 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-42713452014-12-20 Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study Karwowski, Mateusz P Just, Allan C Bellinger, David C Jim, Rebecca Hatley, Earl L Ettinger, Adrienne S Hu, Howard Wright, Robert O Environ Health Research BACKGROUND: Given the relationship between iron metabolism and lead toxicokinetics, we hypothesized that polymorphisms in iron metabolism genes might modify maternal-fetal lead transfer. The objective of this study was to determine whether maternal and/or infant transferrin (TF) and hemochromatosis (HFE) gene missense variants modify the association between maternal blood lead (MBL) and umbilical cord blood lead (UCBL). METHODS: We studied 476 mother-infant pairs whose archived blood specimens were genotyped for TF P570S, HFE H63D and HFE C282Y. MBL and UCBL were collected within 12 hours of delivery. Linear regression models were used to examine the association between log-transformed MBL and UCBL, examine for confounding and collinearity, and explore gene-environment interactions. RESULTS: The geometric mean MBL was 0.61 μg/dL (range 0.03, 3.2) and UCBL 0.42 (<0.02, 3.9). Gene variants were common with carrier frequencies ranging from 12-31%; all were in Hardy-Weinberg equilibrium. In an adjusted linear regression model, log MBL was associated with log UCBL (β = 0.92, 95% CI: 0.82, 1.03; p < 0.01) such that a 1% increase in MBL was associated with a 0.92% increase in UCBL among infants born to wild-type mothers. In infants born to C282Y variants, however, a 1% increase in MBL is predicted to increase UCBL 0.65% (β(Main Effect) = −0.002, 95% CI: −0.09, −0.09; p = 0.97; β(Interaction) = −0.27, 95% CI: −0.52, −0.01; p = 0.04), representing a 35% lower placental lead transfer among women with MBL 5 μg/dL. CONCLUSIONS: Maternal HFE C282Y gene variant status is associated with greater reductions in placental transfer of lead as MBL increases. The inclusion of gene-environment interaction in risk assessment models may improve efforts to safeguard vulnerable populations. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/1476-069X-13-77) contains supplementary material, which is available to authorized users. BioMed Central 2014-10-06 /pmc/articles/PMC4271345/ /pubmed/25287020 http://dx.doi.org/10.1186/1476-069X-13-77 Text en © Karwowski et al.; licensee BioMed Central Ltd. 2014 This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Karwowski, Mateusz P Just, Allan C Bellinger, David C Jim, Rebecca Hatley, Earl L Ettinger, Adrienne S Hu, Howard Wright, Robert O Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study |
title | Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study |
title_full | Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study |
title_fullStr | Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study |
title_full_unstemmed | Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study |
title_short | Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study |
title_sort | maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4271345/ https://www.ncbi.nlm.nih.gov/pubmed/25287020 http://dx.doi.org/10.1186/1476-069X-13-77 |
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