Maternal iron metabolism gene variants modify umbilical cord blood lead levels by gene-environment interaction: a birth cohort study

Environmental Health

Research

Adrienne S Ettinger¹  Allan C Just²  David C Bellinger³  Robert O Wright⁴  Mateusz P Karwowski⁵  Howard Hu⁶  Rebecca Jim⁷  Earl L Hatley⁷ 

[1] Department of Chronic Disease Epidemiology, Center for Perinatal, Pediatric, and Environmental Epidemiology, Yale School of Public Health, New Haven, CT, USA;Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA;Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA;Department of Neurology, Boston Children’s Hospital, Boston, MA, USA;Departments of Preventive Medicine and Pediatrics, Icahn School of Medicine at Mt. Sinai, New York, NY, USA;Division of General Pediatrics, Pediatric Environmental Health Center, Boston Children’s Hospital, Boston, MA, USA;Department of Environmental Health, Harvard School of Public Health, Boston, MA, USA;Divisions of Clinical Public Health, Epidemiology, Global Health, and Occupational and Environmental Health, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario, Canada;Local Environmental Action Demanded Agency, Inc., Miami, OK, USA;

关键词: Hemochromatosis gene;    C282Y;    H63D;    Lead;    Pediatric;    Polymorphism;    Prenatal;    P570S;    Transferrin gene;   

DOI  :  10.1186/1476-069X-13-77

 received in 2014-03-14, accepted in 2014-09-26,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundGiven 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).MethodsWe 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.ResultsThe 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% (βMain Effect = −0.002, 95% CI: −0.09, −0.09; p = 0.97; βInteraction = −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.ConclusionsMaternal 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.

【 授权许可】

CC BY   
© Karwowski et al.; licensee BioMed Central Ltd. 2014