Both the environment and genes are important for concentrations of cadmium and lead in blood

Concentrations of cadmium and lead in blood (BCd and BPb, respectively) are traditionally used as biomarkers of environmental exposure. We estimated the influence of genetic factors on these markers in a cohort of 61 monozygotic and 103 dizygotic twin pairs (mean age = 68 years, range = 49-86). BCd and BPb were determined by graphite furnace atomic absorption spectrophotometry. Variations in both BCd and BPb were influenced by not only environmental but also genetic factors. Interestingly, the genetic influence was considerably greater for nonsmoking women (h(2) = 65% for BCd and 58% for BPb) than for nonsmoking men (13 and 0%, respectively). The shared familial environmental (c(2)) influence for BPb was 37% for men but only 3% for women. The association between BCd and BPb could be attributed entirely to environmental factors of mutual importance for levels of the two metals. Thus, blood metal concentrations in women reflect not only exposure, as previously believed, but to a considerable extent hereditary factors possibly related to uptake and storage. Further steps should focus on identification of these genetic factors and evaluation of whether women are more susceptible to exposure to toxic metals than men.publishedVersio

Spatial and Temporal Variations in Arsenic Exposure via Drinking-water in Northern Argentina

This study evaluated the spatial, temporal and inter-individual variations in exposure to arsenic via drinking-water in Northern Argentina, based on measurements of arsenic in water, urine, and hair. Arsenic concentrations in drinking-water varied markedly among locations, from <1 to about 200 μg/L. Over a 10-year period, water from the same source in San Antonio de los Cobres fluctuated within 140 and 220 μg/L, with no trend of decreasing concentration. Arsenic concentrations in women's urine (3–900 μg/L, specific weight 1.018 g/mL) highly correlated with concentrations in water on a group level, but showed marked variations between individuals. Arsenic concentrations in hair (range 20–1,500 μg/kg) rather poorly correlated with urinary arsenic, possibly due to external contamination. Thus, arsenic concentration in urine seems to be a better marker of individual arsenic exposure than concentrations in drinking-water and hair

Low-Level Environmental Cadmium Exposure Is Associated with DNA Hypomethylation in Argentinean Women

Background: Cadmium, a common food pollutant, alters DNA methylation in vitro. Epigenetic effects might therefore partly explain cadmium’s toxicity, including its carcinogenicity; however, human data on epigenetic effects are lacking

Genetic Polymorphisms Influencing Arsenic Metabolism: Evidence from Argentina

The susceptibility to arsenic-induced diseases differs greatly between individuals, possibly due to interindividual variations in As metabolism that affect retention and distribution of toxic metabolites. To elucidate the role of genetic factors in As metabolism, we studied how polymorphisms in six genes affected the urinary metabolite pattern in a group of indigenous women (n = 147) in northern Argentina who were exposed to approximately 200 μg/L As in drinking water. These women had low urinary percentages of monomethylated As (MMA) and high percentages of dimethylated As (DMA). MMA has been associated with adverse health effects, and DMA has the lowest body retention of the metabolites. The genes studied were arsenic(+III)methyltransferase (AS3MT), glutathione S-transferase omega 1 (GSTO1), 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR), methylenetetrahydrofolate reductase (MTHFR), and glutathione S-transferases mu 1 (GSTM1) and theta 1 (GSTT1). We found three intronic polymorphisms in AS3MT (G12390C, C14215T, and G35991A) associated with a lower percentage of MMA (%MMA) and a higher percentage of DMA (%DMA) in urine. The variant homozygotes showed approximately half the %MMA compared with wild-type homozygotes. These polymorphisms were in strong linkage, with high allelic frequencies (72–76%) compared with other populations. We also saw minor effects of other polymorphisms in the multivariate regression analysis with effect modification for the deletion genotypes for GSTM1 (affecting %MMA) and GSTT1 (affecting %MMA and %DMA). For pregnant women, effect modification was seen for the folate-metabolizing genes MTR and MTHFR. In conclusion, these findings indicate that polymorphisms in AS3MT—and possibly GSTM1, GSTT1, MTR, and MTHFR—are responsible for a large part of the interindividual variation in As metabolism and susceptibility

Spatial and Temporal Variations in Arsenic Exposure via Drinking-water in Northern Argentina

This study evaluated the spatial, temporal and inter-individual variations in exposure to arsenic via drinking-water in Northern Argentina, based on measurements of arsenic in water, urine, and hair. Arsenic concentrations in drinking-water varied markedly among locations, from &lt;1 to about 200 \u3bcg/L. Over a 10-year period, water from the same source in San Antonio de los Cobres fluctuated within 140 and 220 \u3bcg/L, with no trend of decreasing concentration. Arsenic concentrations in women's urine (3-900 \u3bcg/L, specific weight 1.018 g/mL) highly correlated with concentrations in water on a group level, but showed marked variations between individuals. Arsenic concentrations in hair (range 20-1,500 \u3bcg/kg) rather poorly correlated with urinary arsenic, possibly due to external contamination. Thus, arsenic concentration in urine seems to be a better marker of individual arsenic exposure than concentrations in drinking-water and hair

Polymorphisms in Arsenic(+III Oxidation State) Methyltransferase (AS3MT) Predict Gene Expression of AS3MT as Well as Arsenic Metabolism

Background: Arsenic is mono- (MMA) and dimethylated (DMA) in humans and the methylation pattern demonstrates large inter-individual differences. The fraction of urinary MMA is a marker for susceptibility to arsenic-related diseases. Objectives: The impact of polymorphisms in five methyltransferase genes on arsenic metabolism was evaluated in two populations, one in South America, one in southeast Asia. The methyltransferase genes were arsenic(+III)methyltransferase (AS3MT), DNAmethyltransferase 1a and 3b (DNMT1a, DNMT3b), phosphatidylethanolamine Nmethyltransferase (PEMT) and betaine-homocysteine methyltransferase (BHMT). AS3MT expression was analyzed in peripheral blood. Methods: Subjects were women, exposed to arsenic in drinking water in the Argentinean Andes (N=172median urinary arsenic 200 [micro]g/L) and in rural Bangladesh (N=361100g/L, all in early pregnancy). Urinary arsenic metabolites were measured by HPLC-ICPMS. Polymorphisms (N=22) were genotyped with SequenomTM. AS3MT expression was measured with qPCR using TaqManr expression assays. Results: Six AS3MT polymorphisms were significantly associated with arsenic metabolite patterns in both populations (p-values ?0.01). The most frequent AS3MT haplotype in Bangladesh was associated with higher %MMA, and the most frequent in Argentina with lower %MMA and higher %DMA. Four polymorphisms in the DNMTs were associated with metabolite patterns in Bangladesh. Non-coding AS3MT polymorphisms affected gene expression of AS3MT in peripheral blood, demonstrating that one functional impact of AS3MT polymorphisms may be altering levels of gene expression. Conclusions: Polymorphisms in AS3MT significantly predicted As metabolism across these two very different populations, suggesting that AS3MT may have an impact on As metabolite patterns in populations worldwide

Maternal Cadmium Exposure during Pregnancy and Size at Birth: A Prospective Cohort Study

Background: Cadmium (Cd) is an embryotoxic and teratogenic metal in a variety of animal species, but data from humans are limited

Spatial patterns of fetal loss and infant death in an arsenic-affected area in Bangladesh

<p>Abstract</p> <p>Background</p> <p>Arsenic exposure in pregnancy is associated with adverse pregnancy outcome and infant mortality. Knowledge of the spatial characteristics of the outcomes and their possible link to arsenic exposure are important for planning effective mitigation activities. The aim of this study was to identify spatial and spatiotemporal clustering of fetal loss and infant death, and spatial relationships between high and low clusters of fetal loss and infant death rates and high and low clusters of arsenic concentrations in tube-well water used for drinking.</p> <p>Methods</p> <p>Pregnant women from Matlab, Bangladesh, who used tube-well water for drinking while pregnant between 1991 and 2000, were included in this study. In total 29,134 pregnancies were identified. A spatial scan test was used to identify unique non-random spatial and spatiotemporal clusters of fetal loss and infant death using a retrospective spatial and spatiotemporal permutation and Poisson probability models.</p> <p>Results</p> <p>Two significant clusters of fetal loss and infant death were identified and these clusters remained stable after adjustment for covariates. One cluster of higher rates of fetal loss and infant death was in the vicinity of the Meghna River, and the other cluster of lower rates was in the center of Matlab. The average concentration of arsenic in the water differed between these clusters (319 μg/L for the high cluster and 174 μg/L for the low cluster). The spatial patterns of arsenic concentrations in tube-well water were found to be linked with the adverse pregnancy outcome clusters. In the spatiotemporal analysis, only one high fetal loss and infant death cluster was identified in the same high cluster area obtained from purely spatial analysis. However, the cluster was no longer significant after adjustment for the covariates.</p> <p>Conclusion</p> <p>The finding of this study suggests that given the geographical variation in tube-well water contamination, higher fetal loss and infant deaths were observed in the areas of higher arsenic concentrations in groundwater. This illustrates a possible link between arsenic contamination in tube-well water and adverse pregnancy outcome. Thus, these areas should be considered a priority in arsenic mitigation programs.</p