Vitamin D receptor haplotypes affect lead levels during pregnancy.– 2010
Sci Total Environ. 2010 Oct 1;408(21):4955-60. doi: 10.1016/j.scitotenv.2010.07.039. Epub 2010 Aug 6.
Rezende VB1, Amaral JH, Quintana SM, Gerlach RF, Barbosa F Jr, Tanus-Santos JE.
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, 13081-970, Campinas, SP, Brazil.
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.
PMID: 20692022 DOI: 10.1016/j.scitotenv.2010.07.039
Does maternal VDR FokI single nucleotide polymorphism have an effect on lead levels of placenta, maternal and cord bloods? – 2015
Placenta. Volume 36, Issue 8, August 2015, Pages 870-875, https://doi.org/10.1016/j.placenta.2015.06.012
- VDR FokI polymorphism had a significant effect on lead levels in a triad of mother–placenta–fetus.
- Maternal, placental and cord blood lead levels was significantly higher in mothers with VDR FokI Ff + ff genotypes.
- Maternal blood lead was linearly associated with both placental lead and umbilical cord blood lead.
- Fetuses of women with f allele may appear to be disadvantageous for exposing more lead through placenta.
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.
Lead was ADHD risk factor in 16 out of 18 studies – 2016
The Role of Lead Exposure on Attention-Deficit/ Hyperactivity Disorder in Children: A Systematic Review
Iran J Psychiatry. 2016 Jan; 11(1): 1–14.,PMCID: PMC4888135
Objective: Attention-Deficit/Hyperactivity Disorder (ADHD) is one of the most common behavioral disorders in children effecting the families and society. This systematic review examined the literature on the role of lead exposure in children with ADHD symptoms. Articles were analytically compared, focusing on the methodology used to assess exposure and adverse effects on children with ADHD.
Method: Using the search strategy from six databases (Pub Med, PsycINFO, Web of Science, SID, IRAN Medex, IRAN DOC), hand searching in key journals, list of references of selected articles and gray literature, without time and language limitation, articles up to May 2014 were entered into this review. In this review, 1,387 articles were acquired at the primary search. Study selection and quality assessment processes were done based on Cochrane library guidelines. After assessing the quality and inclusion and exclusion criteria, 18 articles were selected and entered into the data synthesis.
Results: Blood Lead level (BLL) of less than 10µg/dL in children has been attributed to at least one type of ADHD i.e., Combined / Inattentive / Hyperactive-Impulsive. The results of this study revealed that in 16 out of the 18 studies, a significant association was found between BLL and one of the types of ADHD.
Conclusion: Based on the findings of this study, even the BLL of less than the action level of 10µg/dL, chosen by Centers for Disease Control and Prevention (CDC), may affect children with ADHD.
Attention deficit / hyperactivity disorder (ADHD) is one of the most commonly diagnosed psychiatric disorders in children. In addition, it is probably the most common chronic condition undiagnosed in adults (1, 2). According to the American Psychiatric Association’s Diagnostic and Statistical Manual Fifth Edition, 3 to 7% of children in school and 2 to 4% of the adult population have ADHD (3, 4).
The global statistics show that about 10.1% of the world’s population has ADHD (5), making this disorder an important health issue. This disorder continues to about 50 to 80% of teenagers and 15 to 65% of adults (6, 7). Moreover, ADHD is more prevalent in boys than girls (9).
Children are more exposed to psychiatric disorders such as
- antisocial personality (9),
- unipolar depression (10),
- bipolar (11),
- learning disabilities,
- emotional disturbance, and
- fiery temperament (9, 12 and 13).
The tendency for drug use and addiction increases in adults if the disorder is not diagnosed and treated at a younger age (14). Some ADHD symptoms disappear with time, but the symptoms such as lack of concentration are constant and a person will be show them throughout their lifetime (13). Therefore, considering the implications, the efforts for early diagnosis of the disease is crucial, and identifying the contributing factors is of prime importance to prevent ADHD.
Biological and environmental factors are the pathogenesis of this disorder, including head injury, a decrease in the prefrontal cortex, and toxins and chemicals found in the environment (15). Although evidence shows that ADHD is a familial problem, many environmental risk factors such as exposure to heavy metals, Dietary factors, environmental exposure to dangerous chemicals such as bisphenol A, polycyclic aromatic compounds, pesticides intensify or accelerate the progression of this disease (16-18).
Lead (Pb) metal as a neurotoxin has been causing abnormal behavior in children, and many studies have examined the relationship between exposure to heavy metals and other harmful environmental factors in the pathogenesis (19-21). Since 1960, the CDC recommended levels for blood lead levels in children have been steadily reduced, and this has been due to increased researches showing that it has negative effects on health. Currently, the children's blood lead level (BLL) is set to 10 micrograms of lead per deciliter of blood (µg/dL), and it has not been changed since 1991 (22). The CDC action level set for lead may be outdated now as recent research indicates that adverse health effects may be associated with blood lead levels below 10µg/dL. Many studies have been conducted on cognitive problems in children including reduced IQ scores, math, reading, verbal memory, and spatial ability, with blood lead levels below 10µg/dL. Recent trends showed a 3% increase in the diagnosis of attention deficit/ hyperactivity disorder (ADHD) in each year from 1997 to 2006 (23). Researchers are investigating whether exposure to lead contributes to an increase in the number of ADHD cases.
A systematic review was conducted to have a clear answer and deep understanding of the topic of concern. Among all the heavy metals, Lead is one of the significant heavy metals causing mental illness. In order to have a clear and deep understanding of the effects of lead on the mental health of children, lead was selected as the main element for the systematic review in this paper. The aim of this study was to systematically review all the studies showing the relationship between ADHD symptoms and blood lead levels below 10µg/dL in children. The findings of these studies also account for the gaps and research needs. Synthesizing the evidence related to ADHD symptoms in children with BLLs less than 10µg/dL will help determine whether the current BLL is still appropriate for children or not.
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