Total Urinary Arsenic Concentration Research Articles

Associations among global long interspersed nuclear element-1 DNA methylation, metal exposure, and chronic kidney disease.

Long interspersed nuclear element-1 (LINE-1) methylation serves as an indicator of global DNA methylation. This study explored the correlation between LINE-1 methylation and chronic kidney disease (CKD). We also evaluated whether LINE-1 methylation could modify the association between CKD and metal exposure. A total of 213 patients with clinically defined CKD, without hemodialysis and 416 age and sex matched controls were recruited. Levels of LINE-1 methylation, total urinary arsenic, blood lead, blood cadmium, and plasma selenium were assessed. The results reveal a positive association between LINE-1 methylation and CKD, with an odds ratio (OR) of 5.30 (95% confidence interval: 2.81 to 9.99). Total urinary arsenic and blood cadmium concentrations were positively related with LINE-1 methylation. This study was the first to observe that low plasma selenium, high blood cadmium, and high blood lead levels significantly and additively interact with increased LINE-1 methylation to increase the OR of CKD. Additionally, high LINE-1 methylation interacted multiplicatively with low plasma selenium to increase the OR of CKD (p < 0.001). This study highlighted the significant association between LINE-1 hypermethylation and CKD. Furthermore, the results demonstrate that LINE-1 methylation can interact with high blood cadmium or low plasma selenium to affect CKD risk.

Interplay of arsenic exposure and cigarette smoking on oxidative DNA damage in healthy males

BackgroundLong-term exposure to inorganic arsenic (As) and cigarette smoking has been associated with adverse health effects such as cancer, cardiovascular disease, and respiratory disease. Oxidative stress is one of the most well-known damage mechanisms for both. However, studies on the association with induced 8-hydroxy-2-deoxyguanosine (8-OHdG) in Iran are scarce, with no study on the interactive effect of As exposure and smoking in the literature.ObjectiveThis stratified cross-sectional study aimed to assess urinary and serum 8-OHdG levels in the relation to As exposure from drinking water, smoking and their interaction effect.MethodsThis study was based on 132 healthy male subjects living in villages of Hashtroud County, Iran (2021). All participants were categorized into four groups: (i) non-As exposed, never smokers (n = 33); (ii) non-As exposed, active smokers (n = 33); (iii) As exposed, never smokers (n = 33); and (iv) As exposed, active smokers (n = 33). Data on demographic and lifestyle factors were collected, and urinary and serum levels of 8-OHdG were determined by enzyme-linked immunosorbent assay (ELISA). The smoker's daily cigarette consumption and the duration of smoking were self-reported data.ResultsParticipants consuming drinking water with an As concentration > 10 µg/L had significantly higher urinary total arsenic (U-tAs) concentrations (median 26.96, IQR 21.35–37.17) µg/g Cr compared to the reference group (median 19.33, IQR 17.29–23.26) µg/g Cr. There was a significant difference in the serum concentration of 8-OHdG between groups (i) and (iii), (iv) and also between groups (ii) and (iv). We did not find a significant interaction effect of As exposure and smoking on the both urinary and serum 8-OHdG levels (P > 0.05). Serum 8-OHdG (S-8OHdG) was associated with average daily intake of As (As-ADI) (β = 0.32; 95% CI 0.01, 0.04, P-value = 0.001) and cigarettes smoked per day (β = 0.3; 95% CI 0.00, 0.043, P-value = 0.046). While As-ADI (β = 0.16; 95% CI 0.001, 0.004, P-value = 0.01) and U-tAs (β = 0.6; 95% CI 0.006, 0.009, P-value < 0.001) were associated with increased urinary 8-OHdG (U-8OHdG), moderate physical activity (β = − 0.15; 95% CI − 0.07, − 0.008, P-value < 0.015) inversely decreased biomarker levels.ConclusionOur findings suggest that As exposure and smoking are potential risk factors for oxidative DNA damage, and it is strongly recommended to pay more attention to the role of lifestyle factors in future studies.

Association of arsenic exposure with measles antibody titers in US children: Influence of sex and serum folate levels

Exposure to arsenic during childhood is associated with various adverse health conditions. However, little is known about the effect of arsenic exposure on vaccine-related humoral immunity in children. We analyzed data from the National Health and Nutrition Examination Survey (2003–2004 and 2009–2010) to study the relationship between urinary arsenic and measles antibody levels in 476 US children aged 6–11. Multivariable linear regression was used to evaluate the association, adjusting for cycle, age, race, body mass index (BMI), serum cotinine, poverty index ratio, and vitamin B12 and selenium intakes. Stratified analyses were conducted by sex and serum folate levels using the median as cutoff (18.7 ng/mL). The measles antibody concentrations in the 3rd and 4th quartiles were found to have significantly decreased by 28.5 % (95 % Confidence Interval (CI) −47.6, −2.28) and 36.8 % (95 % CI −50.2, −19.5), compared to the lowest quartile among boys with serum folate levels lower than 18.7 ng/ml. The serum measles antibody titers significantly decreased by 16.7 % (95 %CI −25.0, −7.61) for each doubling of creatinine-corrected urinary total inorganic arsenic concentrations in the same group. No associations were found in boys with high serum folate levels or in girls. Further prospective studies are needed to validate these findings and develop interventions to protect children from infectious diseases.

Additive interaction of urinary total arsenic concentrations with being overweight/obesity on the risk of insulin resistance: NHANES 2007-2016.

Arsenic exposure has been associated with the risk of diabetes or insulin resistance (IR), which are also related with overweight/obesity. This study aimed to explore the interaction between arsenic exposure and being overweight/obesity on diabetes or IR risk. Data from the National Health and Nutrition Examination Survey (NHANES) in cycles 2007-2016 were used to assess the interaction between arsenic exposure and being overweight/obesity on IR or diabetes risk among adults. Urinary total arsenic concentrations (UTAs) were used as a biomarker for arsenic exposure. The homeostasis model of insulin resistance (HOMA-IR) was calculated to index IR. Survey-weighted logistic regression and restricted cubic spline (RCS) analyses were performed to determine the association and dose-response relationship between UTAs and IR or diabetes risk. Additive interaction was evaluated by relative excess risk due to interaction (RERI), attributable proportion of interaction (AP), and synergy index (S). A total of 3,133 participants were included. The median (interquartile range) UTAs were 6.61 (3.83, 13.95) μg/L. The adjusted OR of IR was 1.40 (95% CI: 0.99-1.97) for UTAs, comparing the highest with the lowest quartile. And significant additive interaction was observed between high UTAs and being overweight/obesity on IR risk (RERI = 2.47, 95% CI: 0.30-4.63; AP = 0.29, 95% CI: 0.07-0.50; S = 1.48, 95% CI: 1.03-2.13). Our results suggested that there might be a potential additive interaction between high UTAs with being overweight/obesity on diabetes risk (AP = 0.27, 95%CI: 0.04-0.51). Our results indicated an additive interaction between arsenic exposure and being overweight/obesity on IR risk.

Metabolic Changes and Their Associations with Selected Nutrients Intake in the Group of Workers Exposed to Arsenic.

Arsenic (As) exposure causes numerous adverse health effects, which can be reduced by the nutrients involved in the metabolism of iAs (inorganic As). This study was carried out on two groups of copper-smelting workers: WN, workers with a urinary total arsenic (tAs) concentration within the norm (n = 75), and WH, workers with a urinary tAs concentration above the norm (n = 41). This study aimed to analyze the association between the intake level of the nutrients involved in iAs metabolism and the signal intensity of the metabolites that were affected by iAs exposure. An untargeted metabolomics analysis was carried out on urine samples using liquid chromatography-mass spectrometry, and the intake of the nutrients was analyzed based on 3-day dietary records. Compared with the WN group, five pathways (the metabolism of amino acids, carbohydrates, glycans, vitamins, and nucleotides) with twenty-five putatively annotated metabolites were found to be increased in the WH group. In the WN group, the intake of nutrients (methionine; vitamins B2, B6, and B12; folate; and zinc) was negatively associated with six metabolites (cytosine, D-glucuronic acid, N-acetyl-D-glucosamine, pyroglutamic acid, uridine, and urocanic acid), whereas in the WH group, it was associated with five metabolites (D-glucuronic acid, L-glutamic acid, N-acetyl-D-glucosamine, N-acetylneuraminic acid, and uridine). Furthermore, in the WH group, positive associations between methionine, folate, and zinc intake and the signal intensity of succinic acid and 3-mercaptolactic acid were observed. These results highlight the need to educate the participants about the intake level of the nutrients involved in iAs metabolism and may contribute to further considerations with respect to the formulation of dietary recommendations for people exposed to iAs.

Arsenic exposure induces urinary metabolome disruption in Pakistani male population

Millions of people are at risk of consuming arsenic (As) contaminated drinking water in Pakistan. The current study aimed to investigate urinary arsenic species [iAsIII, iAsV, dimethylarsinic acid (DMA), methylarsonic acid (MMA)] and their potential toxicity biomarkers (based on urinary metabolome) in order to characterize the health effects in general adult male participants (n = 588) exposed to various levels of arsenic in different floodplain areas of Pakistan. The total urinary arsenic concentration (mean; 161 μg/L) of studied participants was lower and/or comparable than those values reported from other highly contaminated regions, but exceeded the Agency for Toxic Substances and Disease Registry (ATSDR) limits. For all the participants, the most excreted species was DMA accounting for 65% of the total arsenic, followed by MMA (20%) and iAs (16%). The percentage of MMA detected in this study was higher than those of previously reported data from other countries. These results suggested that studied population might have high risk of developing arsenic exposure related adverse health outcomes. Furthermore, random forest machine learning algorithm, partial correlation and binary logistic regression analysis were performed to screen the arsenic species-related urinary metabolites. A total of thirty-eight metabolites were extracted from 2776 metabolic features and identified as the potential arsenic toxicity biomarkers. The metabolites were mainly classified into xanthines, purines, and amino acids, which provided the clues linking the arsenic exposure with oxidative stress, one-carbon metabolism, purine metabolism, caffeine metabolism and hormone metabolism. These results would be helpful to develop early health warning system in context of arsenic exposure among the general populations of Pakistan.

Alterations in Microbial-Associated Fecal Metabolites in Relation to Arsenic Exposure Among Infants.

In utero and early life exposure to inorganic arsenic (iAs) alters immune response in experimental animals and is associated with an increased risk of infant infections. iAs exposure is related to differences in the gut microbiota diversity, community structure, and the relative abundance of individual microbial taxa both in laboratory and human studies. Metabolomics permits a direct measure of molecular products of microbial and host metabolic processes. We conducted NMR metabolomics analysis on infant stool samples and quantified the relative concentrations of 34 known microbial-related metabolites. We examined these metabolites in relation to both in utero and infant log2 urinary total arsenic concentrations (utAs, the sum of iAs and iAs metabolites) collected at approximately 6 weeks of age using linear regression models, adjusted for infant sex, age at sample collection, type of delivery (vaginal vs. cesarean section), feeding mode (breast milk vs. any formula), and specific gravity. Increased fecal butyrate (b = 214.24), propionate (b = 518.33), cholate (b = 8.79), tryptophan (b= 14.23), asparagine (b = 28.80), isoleucine (b = 65.58), leucine (b = 95.91), malonate (b = 50.43), and uracil (b = 36.13), concentrations were associated with a doubling of infant utAs concentrations (p< 0.05). These associations were largely among infants who were formula fed. No clear associations were observed with maternal utAs and infant fecal metabolites. Metabolomic analyses of infant stool samples lend further evidence that the infant gut microbiota is sensitive to As exposure, and these effects may have functional consequences.

Variation in Arsenic metabolism in schistosomiasis associated bladder pathology in a rural community, Eggua, Ogun State, Nigeria

Exposure to toxic inorganic Arsenic (iAs) in areas endemic for urogenital schistosomiasis may confer increased risk for bladder cancer. The severity of the adverse effects of iAs however depends on its metabolism, which is highly variable among individuals. Genetic polymorphism in Arsenic (+3) Methyl Transferase enzyme, accounts significantly for these variations. To investigate the relationship of AS3MT gene polymorphisms and Arsenic metabolism to schistosomiasis and/or associated bladder pathology, 119 individualsfrom Eggua in southwest Nigeria were recruited for this study. Screening for schistosomiasis and bladder pathology was done by microscopy and ultrasonography respectively. Wagtech Digital Arsenator was used to assess total urinary arsenic concentrations and thus determine the level of arsenic exposure. The single nucleotide polymorphism AS3MT/Met287Thr T&gt;C (rs11191439) was genotyped using Alelle-Specific PCR. Of the participants who tested positive for schistosomiasis, 33.3% exhibited bladder pathology. Total urinary arsenic concentration in 80% of the participants was above the WHO limit of 0.05mg/L. The Met287Thr allelic distribution conformed to the Hardy-Weinberg equilibrium (X2= 0.161, P&gt; 0.05). Observed allelic frequencies were 0.96 and 0.04 for wild-type T and mutant C alleles respectively. There was no significant relationship between AS3MT SNP, arsenic concentrations and schistosomiasis associated bladder pathology. In conclusion, the community is highly exposed to arsenic, although with a possible genetic advantage of increased AS3MT catalytic activity. However, we see the need for urgent intervention as inter-individual differences in arsenic metabolism may influence the bladder pathology status of individuals in the community. And although urogenital schistosomiasis is waning in Eggua, it is not known what synergy the infection and high arsenic exposure may wield on bladder pathology.

Arsenic Secondary Methylation Capacity Is Inversely Associated with Arsenic Exposure-Related Muscle Mass Reduction.

Skeletal muscle mass reduction has been implicated in insulin resistance (IR) that promotes cardiometabolic diseases. We have previously reported that arsenic exposure increases IR concomitantly with the reduction of skeletal muscle mass among individuals exposed to arsenic. The arsenic methylation capacity is linked to the susceptibility to some arsenic exposure-related diseases. However, it remains unknown whether the arsenic methylation capacity affects the arsenic-induced reduction of muscle mass and elevation of IR. Therefore, this study examined the associations between the arsenic methylation status and skeletal muscle mass measures with regard to IR by recruiting 437 participants from low- and high-arsenic exposure areas in Bangladesh. The subjects’ skeletal muscle mass was estimated by their lean body mass (LBM) and serum creatinine levels. Subjects’ drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and the percentages of MMA, as well as inversely associated with the percentages of DMA and the secondary methylation index (SMI). Subjects’ LBM and serum creatinine levels were positively associated with the percentage of DMA and SMI, as well as inversely associated with the percentage of MMA. HOMA-IR showed an inverse association with SMI, with a confounding effect of sex. Our results suggest that reduced secondary methylation capacity is involved in the arsenic-induced skeletal muscle loss that may be implicated in arsenic-induced IR and cardiometabolic diseases.

The relatively higher concentrations of trace elements to arsenic may have influenced on methylation process of inorg- As in humans

The relatively higher concentrations of trace elements to arsenic may have influenced on methylation process of inorg- As in humans

Abstract 857: Evaluating the relationship between arsenic exposure and cancer risk in Canada

Abstract Background: Arsenic is an established carcinogen for cancers of the skin, bladder and lungs; it is also the most prevalent environmental toxin, resulting in all Canadians being exposed to some extent. In a recent prospective study of a low-exposure population, our team found that women in the highest quartile of circulating arsenic had a significant 13-fold increased risk of developing breast cancer, compared to the lowest quartile. This suggests that even at low-doses, arsenic may be an important risk factor for breast, and potentially other cancers not previously recognized. To date, the sources of arsenic in Canada, a low-exposure population, are unclear. Objectives: To describe the status of arsenic exposure, identify the key predictors of arsenic status, and evaluate the relationship between arsenic exposure and cancer risk within the Canadian population. Methods: Using data from Cycles 1-5 (2007-2017) of the Canadian Health Measures Survey (CHMS), exposure data (e.g., diet, water), demographic information, and urinary arsenic biomarkers will be analyzed. The CHMS is an ongoing, nationally representative survey, collecting objective health measures and food intake information from participants in biennial cycles. Data will be described using weighted percentages or means, and arsenic levels (total and speciated urinary arsenic metabolite concentrations) will be reported by percentile. Weighted multivariate regression models will be used to identify predictors of total urinary arsenic. Linkage to the Canadian Cancer Registry will be performed to ascertain incident cancers, and Cox proportional hazards regression used to estimate the relationship between arsenic status and cancer risk (total and site-specific). Results: This analysis included 15,700 individuals, aged 18-80. The median total urinary arsenic level was 7.5 ug/g of creatinine. Significant predictors of total urinary arsenic levels were found to be weekly intake of fish and seafood (β= 0.3, 95%CI 0.27,0.33, P &amp;lt; 0.001), grains (β=-0.02, 95%CI -0.02, -0.01, P&amp;lt; 0.001) and consumption of well and/or cistern water (β = 0.13, 95%CI 0.04, 0.22, P=0.005). Linkage and data analysis are ongoing. Impact: This work is the first to ascertain national exposure estimates to an environmental carcinogen. Fish, seafood, grains, and consumption of well and/or cistern water represent significant predictors of total urinary arsenic levels in Canada. Ultimately, this information is needed to develop critical population-level intervention strategies to reduce the Canadian, and global burden of cancer. Citation Format: Katherine Pullella, Shelley A. Harris, John R. McLaughlin, Jan Lubinski, Steven A. Narod, Joanne Kotsopoulos. Evaluating the relationship between arsenic exposure and cancer risk in Canada [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 857.

Rare, Protein-Altering Variants in AS3MT and Arsenic Metabolism Efficiency: A Multi-Population Association Study.

Background:Common genetic variation in the arsenic methyltransferase (AS3MT) gene region is known to be associated with arsenic metabolism efficiency (AME), measured as the percentage of dimethylarsinic acid (DMA%) in the urine. Rare, protein-altering variants in AS3MT could have even larger effects on AME, but their contribution to AME has not been investigated.Objectives:We estimated the impact of rare, protein-coding variation in AS3MT on AME using a multi-population approach to facilitate the discovery of population-specific and shared causal rare variants.Methods:We generated targeted DNA sequencing data for the coding regions of AS3MT for three arsenic-exposed cohorts with existing data on arsenic species measured in urine: Health Effects of Arsenic Longitudinal Study (HEALS, ), Strong Heart Study (SHS, ), and New Hampshire Skin Cancer Study (NHSCS, ). We assessed the collective effects of rare (allele frequency ), protein-altering AS3MT variants on DMA%, using multiple approaches, including a test of the association between rare allele carrier status (yes/no) and DMA% using linear regression (adjusted for common variants in 10q24.32 region, age, sex, and population structure).Results:We identified 23 carriers of rare-protein-altering AS3MT variant across all cohorts (13 in HEALS and 5 in both SHS and NHSCS), including 6 carriers of predicted loss-of-function variants. DMA% was 6–10% lower in carriers compared with noncarriers in HEALS [ (95% CI: , )], SHS [ (95% CI: , )], and NHSCS [ (95% CI: , )]. In meta-analyses across cohorts, DMA% was 8.7% lower in carriers [ (95% CI: , )].Discussion:Rare, protein-altering variants in AS3MT were associated with lower mean DMA%, an indicator of reduced AME. Although a small percentage of the population (0.5–0.7%) carry these variants, they are associated with a 6–10% decrease in DMA% that is consistent across multiple ancestral and environmental backgrounds. https://doi.org/10.1289/EHP8152

Cohort profile: health effects monitoring programme in Ndilǫ, Dettah and Yellowknife (YKHEMP)

PurposeThe Yellowknife Health Effects Monitoring Programme (YKHEMP) was established to examine the relationship of exposure to arsenic and other chemicals of potential concern such as antimony, cadmium, lead, manganese and...

Effect of plasma selenium, red blood cell cadmium, total urinary arsenic levels, and eGFR on renal cell carcinoma

High total urinary arsenic concentrations and low estimated glomerular filtration rate (eGFR) increase the risk of renal cell carcinoma (RCC). This study aimed to determine whether other metals or metalloids can affect RCC. A total of 401 patients with RCC and 774 age- and sex-matched controls were recruited between November 2006 and December 2012 in Taiwan. Surgical resection or image-guided biopsy of renal tumors was performed to pathologically verify RCC. High-performance liquid chromatography linked to a hydride generator and atomic absorption spectrometer were used to measure the urinary arsenic species concentrations. Inductively coupled plasma mass spectrometry was used to determine plasma selenium and red blood cell cadmium and lead concentration. Plasma selenium levels were inversely related to RCC, whereas red blood cell cadmium levels were directly related to RCC. The odds ratio (OR) and 95% confidence interval (CI) were 0.14 (95% CI, 0.10–0.20) and 1.33 (95% CI, 1.03–1.72), respectively. A low plasma selenium level tended to interact with high total urinary arsenic levels or with high red blood cell cadmium concentration to increase the OR of RCC. In particular, low eGFR multiplicatively interacted with high red blood cell cadmium concentration to increase the OR of RCC (Pinteraction=0.003). This study was the first to find a significant multiplicative interaction between eGFR and the red blood cell cadmium levels on the increased OR of RCC.

Vitamin B-6 Intake Is Modestly Associated with Arsenic Methylation in Uruguayan Children with Low-Level Arsenic Exposure

Background:Detoxification of inorganic arsenic (iAs) occurs when it methylates to form monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA). Lower proportions of urinary iAs and MMA, and higher proportions of DMA indicate efficient methylation. The role of B-vitamins in iAs methylation in children with low-level arsenic exposure is understudied. Objectives:Our study objective was to assess the association between B-vitamin intake and iAs methylation in children with low-level arsenic exposure (<50 µg/L in water; urinary arsenic 5–50 µg/L). Methods:We conducted a cross-sectional study in 290 ~7-y-old children in Montevideo. Intake of thiamin, riboflavin, niacin, vitamin B-6, and vitamin B-12 was calculated by averaging 2 nonconsecutive 24-h recalls. Total urinary arsenic concentration was measured as the sum of urinary iAs, MMA, and DMA, and adjusted for urinary specific gravity; iAs methylation was measured as urinary percentage As, percentage MMA, and percentage DMA. Arsenic concentrations from household water sources were assessed. Linear regressions tested the relationships between individual energy-adjusted B-vitamins and iAs methylation. Results:Median (range) arsenic concentrations in urine and water were 9.9 (2.2–48.7) and 0.45 (0.1–18.9) µg/L, respectively. The median (range) of urinary percentage iAs, percentage MMA, and percentage DMA was 10.6% (0.0–33.8), 9.7% (2.6–24.8), and 79.1% (58.5–95.4), respectively. The median (range) intake levels of thiamin, riboflavin, niacin, and vitamin B-6 were 0.81 (0.19–2.56), 1.0 (0.30–2.24), 8.6 (3.5–23.3), and 0.67 (0.25–1.73) mg/1000 kcal, respectively, whereas those of folate and vitamin B-12 were 216 (75–466) and 1.7 (0.34–8.3) µg/1000 kcal, respectively. Vitamin B-6 intake was inversely associated with urinary percentage MMA (β = –1.60; 95% CI: –3.07, –0.15). No other statistically significant associations were observed. Conclusions:Although vitamin B-6 intake was inversely associated with urinary percentage MMA, our findings suggest limited support for a relation between B-vitamin intake and iAs methylation in children exposed to low-level arsenic.

Polymorphism of nucleotide binding domain-like receptor protein 3 (NLRP3) increases susceptibility of total urinary arsenic to renal cell carcinoma

Our study showed that total urinary arsenic concentrations were positively correlated with renal cell carcinoma (RCC). Chronic inflammation is a key player in the development of RCC. This study explored the association between nucleotide-binding domain-like receptor protein 3 (NLRP3) genotypes and the development of RCC. We also investigated whether any of the NLRP3 genotypes modified the risk between arsenic and RCC. We recruited 350 RCC patients and 700 age-sex matched controls. RCC was confirmed by pathological assessment following surgical resection or image-guided biopsy of a renal tumor. Fifteen sites of NLRP3 gene polymorphisms were identified using the Agena Bioscience MassARRAY platform. The concentrations of the urinary arsenic species were determined by HPLC-HG-AAS. There was a significant dose-dependent association between arsenic and RCC. In addition, six of thirteen NLRP3 alleles, including rs12239046 C, rs10925025 G, rs1539019 C, rs10925026 A, rs10157379 T, and rs12143966 A, had increased odds ratios (ORs) for RCC than other NLRP3 alleles. Among these sites, we found the novel haplotype of five tag-SNPs (C-A-A-A-A) was significantly related to RCC, the OR and 95% confidence interval was 1.44 (1.08–1.92). Furthermore, participants with high total urinary arsenic levels and the NLRP3 rs1539019 C allele had significantly multiplicative and additive interactions for the risk of RCC (p interaction = 0.012). This study is the first to identify the modified effects of NLRP3 risk alleles involved in the association between arsenic and RCC risk in a population with low arsenic exposure.

Arsenic Exposure and Association with Hepatitis E IgG Antibodies

Arsenic is a known toxic chemical, has immuno-modulatory properties, and can change the susceptibility of infection in humans. Acute hepatitis E is an infectious disease; it can be self-limiting, but in severe cases, can cause acute-on-chronic liver failure. The presence of IgG anti-HEV (hepatitis E IgG antibody) in blood represents a past hepatitis E infection in an individual. Very few studies have investigated the association between arsenic levels and hepatitis E seroconversion in humans. The primary objective of this study was to assess the relationship between total urinary arsenic and speciated urinary arsenic (urinary arsenous acid, urinary arsenic acid, urinary arsenobetaine, urinary arsenocholine, urinary dimethylarsinic acid, urinary monomethylarsonic acid) and the presence of IgG anti-HEV. The 2011-2012, 2013-2014, and 2015-2016 National Health and Nutrition Examination Survey (NHANES) III data sets were analyzed, with participants aged 20 years and older (n = 7061). We used weighted logistic regression to determine the association between total and speciated urinary arsenic concentrations and IgG anti-HEV. For each analyte considered, a separate weighted logistic regression model was fitted. Each of these models regressed log-transformed analyte levels on the log-odds of the presence of IgG Anti-HEV. To evaluate the relationships between the urinary arsenic measurements, pairwise Pearson correlation coefficients were determined for each of the urinary arsenic measurements. Of the human subjects included, 6628 (93.9%) were negative for IgG Anti-HEV while 433 (6.1%) were positive for IgG anti-HEV. Total urinary arsenic was associated with 1.161 times greater odds of IgG anti-HEV (95% CI: [1.035, 1.303]) for each unit increase in concentration on a log-scale. For speciated urinary arsenic measurements, the odds ratios and 95% CI’s were: arsenobetanine 1.168 [1.075, 1.270], arsenocholine 1.201 [0.944, 1.529], dimethylarsinic acid 1.183 [1.009, 1.386], monomethylacrsonic acid 1.095 [0.915, 1.310], aresnous acid 0.907 [0.762, 1.079], and arsenic acid 1.951 [0.905, 4.209]. Our analysis indicates that total urinary arsenic, arsenobetanine, and dimethylarsinic acid are significantly associated with the odds of the presence of IgG anti-HEV. Future prospective studies are required to evaluate the association between hepatitis E infection and arsenic exposures.

A Study of urinary total arsenic concentration and its effect on health in industrial areas

A Study of urinary total arsenic concentration and its effect on health in industrial areas

The association between plasma selenium and chronic kidney disease related to lead, cadmium and arsenic exposure in a Taiwanese population.

This study aimed to determine the interaction of red blood cell cadmium and lead, total urinary arsenic, and plasma selenium in chronic kidney disease (CKD). We recruited 220 CKD patients as well as 438 gender- and age-matched controls, and we defined CKD as <60 mL/min/1.73 m2 estimated glomerular filtration rate (eGFR) for three or more consecutive months. Plasma selenium and red blood cell cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined via HPLC-HG-AAS and were summed to determine the total urinary arsenic concentration. Plasma selenium was positively correlated to eGFR, and subjects with high plasma selenium levels (>243.90 μg/L) had a significantly lower odds ratio (OR) and 95% confidence interval (CI) (0.23, 0.13-0.42) for CKD compared to those with low plasma selenium levels (≤ 196.70 μg/L). High plasma selenium and low red blood cell cadmium or lead concentrations interacted to decrease the OR and 95% CI for CKD (0.12, 0.06-0.26; 0.09, 0.04-0.19). High plasma selenium and low red blood cell lead levels also interacted to increase the eGFR (20.70, 15.56-26.01 mL/min/1.73 m2). This study is the first to suggest that selenium modifies the eGFR and OR in CKD induced by environmental toxicants.

Comparison of arsenic methylation capacity and polymorphisms of arsenic methylation genes between bladder cancer and upper tract urothelial carcinoma

Arsenic exposure is an environmental risk factor for urothelial carcinoma (UC). The natural history of upper tract urothelial carcinoma (UTUC) differs from that of bladder cancer (BC). However, the risk factors of BC and UTUC are not exactly the same and should be discussed separately. The aims of this study were to evaluate 1) the association between arsenic methylation capacity and UTUC and/or BC, separately, and 2) the association between polymorphisms of the arsenic metabolism-related genes AS3MT, GSTOs, and PNP against BC and/or UTUC, separately. We conducted a hospital-based study and collected 216 BC and 212 UTUC cases, and 813 healthy controls, from September 2007 to October 2011. Urinary arsenic profiles were measured using high-performance liquid chromatography-hydride generator-atomic absorption spectrometry. The polymorphisms of AS3MT, GSTO, and PNP were identified using the Sequenom MassARRAY platform with iPLEX Gold chemistry. We found that inefficient arsenic methylation capacity was associated with BC in a significant dose-response relationship, but only found that high urinary total arsenic concentration was related to the risk of UTUC, also in a significant dose-response manner. Those with a total urinary arsenic level of > 30.28 μg/L compared to ≤ 9.78 μg/L, had a odds ratio (OR), and 95% confidence interval (CI) of UTUC, of 4.80 (2.22–10.39). The polymorphisms of AS3MT rs11191438, AS3MT rs10748835, and AS3MT rs1046778 were related to the risk of BC and UTUC, while the polymorphisms of AS3MT rs3740393, AS3MT rs11191453, and AS3MT rs11191454 were associated with arsenic methylation capacity. The AS3MT gene polymorphisms and arsenic methylation capacity appear to independently affect the risk of BC and UTUC.