scholarly journals As3MT and GST Polymorphisms Influencing Arsenic Metabolism in Human Exposure to Drinking Groundwater

2020 ◽  
Vol 21 (14) ◽  
pp. 4832 ◽  
Author(s):  
Farith González-Martínez ◽  
Daniel Sánchez-Rodas ◽  
Nelson M. Varela ◽  
Christopher A. Sandoval ◽  
Luis A. Quiñones ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Multivariate Analyses ◽  
Arsenic Concentration ◽  
Human Consumption ◽  
Dimethylarsinic Acid ◽  
Wild Type ◽  
High Exposure ◽  
Urinary Arsenic ◽  
Polymorphic Variants ◽  
Arsenic Metabolites

The urinary arsenic metabolites may vary among individuals and the genetic factors have been reported to explain part of the variation. We assessed the influence of polymorphic variants of Arsenic-3-methyl-transferase and Glutathione-S-transferase on urinary arsenic metabolites. Twenty-two groundwater wells for human consumption from municipalities of Colombia were analyzed for assessed the exposure by lifetime average daily dose (LADD) (µg/kg bw/day). Surveys on 151 participants aged between 18 and 81 years old were applied to collect demographic information and other factors. In addition, genetic polymorphisms (GSTO2-rs156697, GSTP1-rs1695, As3MT-rs3740400, GSTT1 and GSTM1) were evaluated by real time and/or conventional PCR. Arsenic metabolites: AsIII, AsV, monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA) were measured using HPLC-HG-AFS. The influence of polymorphic variants, LADD and other factors were tested using multivariate analyses. The median of total arsenic concentration in groundwater was of 33.3 μg/L and the median of LADD for the high exposure dose was 0.33 µg/kg bw/day. Univariate analyses among arsenic metabolites and genetic polymorphisms showed MMA concentrations higher in heterozygous and/or homozygous genotypes of As3MT compared to the wild-type genotype. Besides, DMA concentrations were lower in heterozygous and/or homozygous genotypes of GSTP1 compared to the wild-type genotype. Both DMA and MMA concentrations were higher in GSTM1-null genotypes compared to the active genotype. Multivariate analyses showed statistically significant association among interactions gene-gene and gene-covariates to modify the MMA and DMA excretion. Interactions between polymorphic variants As3MT*GSTM1 and GSTO2*GSTP1 could be potential modifiers of urinary excretion of arsenic and covariates as age, LADD, and alcohol consumption contribute to largely vary the arsenic individual metabolic capacity in exposed people.

The Relationship Between Urinary Arsenic Metabolites, Drinking Water, and Genetic Polymorphisms in Glutathione S-transferase M1 and T1

Epidemiology ◽  
2006 ◽  
Vol 17 (Suppl) ◽  
pp. S149-S150 ◽  
Author(s):  
M L. Kile ◽  
E A. Houseman ◽  
T J. Smith ◽  
J J. Harrington ◽  
Q Quamruzzaman ◽  
...  
Keyword(s):  
Drinking Water ◽  
Genetic Polymorphisms ◽  
Glutathione S Transferase ◽  
Urinary Arsenic ◽  
Arsenic Metabolites ◽  
The Relationship

Association of Urinary Arsenic and Sleep Disorder in the U.S. Population: NHANES 2015-2016

2021 ◽  
Author(s):  
Humairat H Rahman ◽  
Danielle Niemann ◽  
Korede K Yusuf
Keyword(s):  
Sleep Disturbance ◽  
Sleep Disorder ◽  
Neurodegenerative Disorder ◽  
Arsenic Concentration ◽  
Arsenic Exposure ◽  
Multivariate Logistic Regression Analysis ◽  
Total Sample ◽  
Dimethylarsinic Acid ◽  
Urinary Arsenic ◽  
Study Participants

Abstract Arsenic is a known carcinogen and neurotoxin and is found in the natural earth crust. Arsenic exposure can develop depression, memory dysfunction, and neurodegenerative disorder. The mechanism of arsenic toxicity on the nervous system is not known. There is a lack of research on the association between arsenic exposure and sleep disturbance in humans. This study aims to investigate the relationship between six types of urinary speciated arsenic exposure and sleep disturbance in adults from the general population using the National Health and Nutrition Examination Survey (NHANES) 2015–2016 dataset. Sleep disturbance was measured using self-reported questionnaires, asking participants if they had ever told a doctor they had trouble sleeping. We utilized multivariate logistic regression analysis using complex survey procedures to examine the association between six types of urinary arsenic concentration and trouble sleeping. The total sample included 1,611 adults who were 20 years and older. Of the study participants, 30.0% had trouble sleeping. Urinary arsenous acid was associated with an increased odds of had trouble sleeping [odds ratio: 1.47 (95% confidence interval 1.02–2.11). The other five types of urinary speciated arsenic (arsenic acid, arsenobetaine, arsenocholine, dimethylarsinic acid, monomethylacrsonic acid) were not associated with a sleep disorder.

scholarly journals Distributive characteristics of the CYP2C9 and AGTR1 genetic polymorphisms in Han Chinese hypertensive patients: a retrospective study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Keping Chen ◽  
Peng Xiao ◽  
Guochun Li ◽  
Chunling Wang ◽  
Chuankun Yang
Keyword(s):  
Genetic Polymorphisms ◽  
Venous Blood ◽  
Gene Chip ◽  
Han Chinese ◽  
Genotype Frequency ◽  
Wild Type ◽  
Angiotensin Ii Receptor ◽  
Hypertensive Patients ◽  
Genotype Frequencies ◽  
Combined Genotypes

Abstract Background There is an individual variation in response to antihypertensive effect of the angiotensin II receptor antagonist. This study aimed to determine the allele and genotype frequencies of CYP2C9 and AGTR1 genetic polymorphisms and explore the potential role of these polymorphisms in guiding the selection of angiotensinIIreceptor antagonist in Han Chinese hypertensive patients. Methods Totally 2419 Han Chinese hypertensive patients and 126 normotensive controls were recruited in this study. Venous blood samples were collected from each patient, and the genetic polymorphisms of CYP2C9 and AGTR1 were assessed using a gene chip platform. The allele and genotype frequency of each gene and the combined genotypes in this study were analyzed respectively. Results The gene chip analysis identified an allelic frequency of 96.51% for CYP2C9*1 and 3.49% for CYP2C9*3 in the cohort of Han Chinese hypertensive patients. Statistical analysis showed that the frequency of wild-type homozygous for CYP2C9*1/*1 was 93.30%, while the frequency of heterozygous for *1/*3 or mutant homozygous for *3/*3 was 6.41% or 0.29%. Meanwhile, we detected allelic frequencies of 95.06% and 4.94% for the A and C allele of AGTR1, respectively. While the genotype frequency of wild-type homozygous for AA was 90.41%, the frequency of heterozygous for AC or mutant homozygous for CC was 9.30% or 0.29%. Notably, we observed that 84.66% (2048/2419) of the subjects exhibited a combined genotype of CYP2C9 and AGTR1 as *1/*1 + AA, while the combined genotypes *3/*3 + AC or *3/*3 + CC were not detected in hypertension patients. Besides, no significant association was found between normotensive controls and hypertensive patients, or among the three grades of hypertensive patients. Conclusions These data revealed the polymorphisms characteristics of CYP2C9 and AGTR1 in Han Chinese hypertensive patients, providing valuable information for genotype-based antihypertension therapy in prospective clinical studies in the future.

scholarly journals Urinary arsenic concentration in a high arsenic area of south west England.

1997 ◽  
Vol 54 (11) ◽  
pp. 840-840 ◽  
Author(s):  
P Kavanagh ◽  
M E Farago ◽  
I Thornton ◽  
P Elliott ◽  
W Goessler ◽  
...  
Keyword(s):  
Arsenic Concentration ◽  
Urinary Arsenic ◽  
South West ◽  
South West England ◽  
High Arsenic

scholarly journals Genetic Polymorphisms in Glutathione (GSH-) Related Genes Affect the Plasmatic Hg/Whole Blood Hg Partitioning and the Distribution between Inorganic and Methylmercury Levels in Plasma Collected from a Fish-Eating Population

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Andréia Ávila Soares de Oliveira ◽  
Marilesia Ferreira de Souza ◽  
André van Helvoort Lengert ◽  
Marcelo Tempesta de Oliveira ◽  
Rossana Batista de Oliveira Godoy Camargo ◽  
...  
Keyword(s):  
Genetic Polymorphisms ◽  
Whole Blood ◽  
Fish Consumption ◽  
Multivariate Analyses ◽  
Mercury Species ◽  
Icp Ms ◽  
Total Hg ◽  
Pcr Assays ◽  
Plasma Compartment

This study aims to evaluate the effects of polymorphisms in glutathione (GSH-) related genes (GSTM1,GSTT1,GSTP1,GCLM, andGCLC) in the distribution of Hg in the blood compartments in humans exposed to methylmercury (MeHg). Subjects (n=88), exposed to MeHg from fish consumption, were enrolled in the study. Hg species in the plasma compartment were determined by LC-ICP-MS, whereas genotyping was performed by PCR assays. Mean total Hg levels in plasma (THgP) and whole blood (THgB) were10±4.2and37±21, whereas mean evels of plasmatic MeHg (MeHgP), inorganic Hg (IHgP), and HgP/HgB were4.3±2.9,5.8±2.3 µg/L, and0.33±0.15, respectively.GSTM1andGCLCpolymorphisms influence THgP and MeHgP (multivariate analyses,P<0.050). Null homozygotes forGSTM1showed higher THgP and MeHgP levels compared to subjects withGSTM1(THgPβ=0.22,P=0.035; MeHgPβ=0.30,P=0.050) and persons carrying at least one T allele forGCLChad significant higher MeHgP (β=0.59,P=0.046). Also, polymorphicGCLMsubjects had lower THgP/THgB than those with the nonvariant genotype. Taken together, data of this study suggest that GSH-related polymorphisms may change the metabolism of MeHg by modifying the distribution of mercury species iin plasma compartment and the HgP/HgB partitioning.

scholarly journals Lys694Arg polymorphism leads to blunted responses to LPS by interfering TLR4 with recruitment of MyD88

2020 ◽  
pp. 175342592092747
Author(s):  
Yajie Yang ◽  
Yan Hu ◽  
Yile Zhou ◽  
Tao Liang ◽  
Haihong Tang ◽  
...  
Keyword(s):  
Inflammatory Factors ◽  
Myeloid Differentiation ◽  
Study Group ◽  
Tlr4 Expression ◽  
Wild Type ◽  
Human Embryonic Kidney ◽  
Gram Negative ◽  
Tnf Α ◽  
Polymorphic Variants ◽  
Myeloid Differentiation Factor

TLR4 polymorphisms such as Asp299Gly and Thr399Ile related to Gram-negative sepsis have been reported to result in significantly blunted responsiveness to LPS. Our study group previously screened other TLR4 polymorphic variants by checking the NF-κB activation in comparison to wild type (WT) TLR4 in human embryonic kidney 293T cells. In this study, we found that the Lys694Arg (K694R) polymorphism reduced the activation of NF-κB, and the production of downstream inflammatory factors IL-1, TNF-α and IL-6, representing the K694R polymorphism, led to blunted responsiveness to LPS. Then, we examined the influence of the K694R polymorphism on total and cell-surface TLR4 expression by Western blotting and flow cytometry, respectively, but observed no differences between the K694R polymorphism and WT TLR4. We also used co-immunoprecipitation to determine the interaction of the K694R polymorphism and WT TLR4 with their co-receptor myeloid differentiation factor 2 (MD2) and their downstream signal adaptor MyD88. We found that K694R reduced the recruitment of MyD88 in TLR4 signalling but had no impact on the interaction with MD2.

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