Vitamin D receptor haplotypes affect lead levels during pregnancy

Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 13081-970, Campinas, SP, Brazil.
Science of The Total Environment (Impact Factor: 4.1). 10/2010; 408(21):4955-60. DOI: 10.1016/j.scitotenv.2010.07.039
Source: PubMed

ABSTRACT Pregnant women are particularly susceptible to toxic effects associated with lead (Pb) exposure. Pb accumulates in bone tissue and is rapidly mobilized from bones during pregnancy, thus resulting in fetal contamination. While vitamin D receptor (VDR) polymorphisms modify bone mineralization and affect Pb biomarkers including blood (Pb-B) and serum (Pb-S) Pb concentrations, and %Pb-S/Pb-B ratio, the effects of these polymorphisms on Pb levels in pregnant women are unknown. This study aimed at examining the effects of three (FokI, BsmI and ApaI) VDR polymorphisms (and VDR haplotypes) on Pb levels in pregnant women. Pb-B and Pb-S were determined by inductively coupled plasma mass spectrometry in samples from 256 healthy pregnant women and their respective umbilical cords. Genotypes for the VDR polymorphisms were determined by PCR and restriction fragment length digestion. While the three VDR polymorphisms had no significant effects on Pb-B, Pb-S or %Pb-S/Pb-B ratio, the haplotype combining the f, a, and b alleles for the FokI, ApaI and BsmI polymorphisms, respectively, was associated with significantly lower Pb-S and %Pb-S/Pb-B (P<0.05). However, maternal VDR haplotypes had no effects on Pb levels in the umbilical cords. To our knowledge, this is the first study showing that a combination of genetic polymorphisms (haplotype) commonly found in the VDR gene affects Pb-S and %Pb-S/Pb-B ratios in pregnant women. These findings may have major implications for Pb toxicity because they may help to predict the existence of a group of subjects that is genetically less prone to Pb toxicity during pregnancy.

    • "Among these previous studies, Pawlas et al. (2012) studied this effect in 175 children and found that VDR FokI polymorphism did not modify the relationship between blood lead and cognitive function in children [26]. In another study, Rezende et al. (2010) examined the effect of three different VDR polymorphisms (FokI, ApaI and BsmI) in 256 healthy pregnant women and detected that these polymorphisms had no effect on blood and serum lead levels, whereas the haplotype combining the f, a, and b alleles for the FokI, ApaI and BsmI polymorphisms, respectively, was associated with lower serum lead level [6]. Haynes et al. (2003) also investigated the association between VDR FokI polymorphism and blood lead concentration in 275 children and determined that VDR FokI modifies this association [28]. "
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    ABSTRACT: Individual susceptibility due to genetic variations appears to be an important factor in lead toxicity. As lead, ubiquitous atmospheric pollutant, behaves very similarly to calcium, gene polymorphisms in proteins involved in calcium homeostasis can affect lead toxicokinetics. Vitamin D receptor (VDR), a DNA-binding transcription factor, activates genes that encode proteins involved in calcium metabolism. Thus, the objective of this study was to determine the effect of maternal VDR FokI polymorphism on lead levels of maternal blood, placental tissue and cord blood. The study population comprised 116 women and their respective placenta and umbilical cord. Venous blood samples were drawn from mothers to investigate both the lead levels and VDR FokI polymorphism. Cord blood samples and placentas were collected for lead levels. VDR FokI polymorphism was detected by standard polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) method. Lead levels were analyzed by dual atomic absorption spectrometer system. Genotype frequencies of VDR FokI polymorphism were 49.2% FF, 44.8% Ff and 6.0% ff. The mean lead levels of maternal blood, placenta and cord blood were 36.76 ± 13.84 μg/L, 12.84 ± 14.47 μg/kg and 25.69 ± 11.12 μg/L, respectively. Maternal blood, placental and cord blood lead levels were found significantly to be higher in mothers with f allele for the VDR FokI polymorphism (p < 0.05). The present study indicated that this polymorphism had an effect on maternal and fetal lead levels and that mothers with F allele associated with lower lead concentration may protect their respective fetus against the toxic effects of lead exposure. Copyright © 2015 Elsevier Ltd. All rights reserved.
    50th Congress of the European Societies of Toxicology, Edinburgh; 09/2014
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    • "During pregnancy, bone turnover increases due to increased demands for calcium. With calcium, accumulated lead removes from bone to blood stream and can easily across the placenta causing increased spontaneous release of neurotransmitters and disruption of calcium metabolism [20]. Lower IQ, reduced frustration tolerance, attention deficit, hyperactivity and weak reaction control are possible neurodevelopmental consequences of lead exposure [21]. "
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    ABSTRACT: Dilek Kaya Akyuzlu, Zeliha Kayaalti, Esma Soylemez and Tulin Soylemezoglu
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    ABSTRACT: Several recent investigations have reported high concentrations of lead in samples of minced cervid meat. This paper describes findings from a Norwegian study performed in 2012 among 147 adults with a wide range of cervid game consumption. The main aim was to assess whether high consumption of lead-shot cervid meat is associated with increased concentration of lead in blood. A second aim was to investigate to what extent factors apart from game consumption explain observed variability in blood lead levels. Median (5 and 95 percentile) blood concentration of lead was 16.6µg/L (7.5 and 39µg/L). An optimal multivariate linear regression model for log-transformed blood lead indicated that cervid game meat consumption once a month or more was associated with approximately 31% increase in blood lead concentrations. The increase seemed to be mostly associated with consumption of minced cervid meat, particularly purchased minced meat. However, many participants with high and long-lasting game meat intake had low blood lead concentrations. Cervid meat together with number of bullet shots per year, years with game consumption, self-assembly of bullets, wine consumption and smoking jointly accounted for approximately 25% of the variation in blood lead concentrations, while age and sex accounted for 27% of the variance. Blood lead concentrations increased approximately 18% per decade of age, and men had on average 30% higher blood lead concentrations than women. Hunters who assembled their own ammunition had 52% higher blood lead concentrations than persons not making ammunition. In conjunction with minced cervid meat, wine intake was significantly associated with increased blood lead. Our results indicate that hunting practices such as use of lead-based ammunition, self-assembling of lead containing bullets and inclusion of lead-contaminated meat for mincing to a large extent determine the exposure to lead from cervid game consumption.
    Environmental Research 10/2013; 127. DOI:10.1016/j.envres.2013.08.007 · 3.95 Impact Factor
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