Associations between the polymorphisms of GSTT1, GSTM1 and methylation of arsenic in the residents exposed to low-level arsenic in drinking water in China

Yang, Jinyou; Li, Yan; Zhang, Min; Wang, Yijun; Chün, Wang; Xiang, Qiaojun

doi:10.1038/jhg.2015.39

Cited by 7 publications

(6 citation statements)

References 23 publications

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“…GSTT1 wild/null polymorphism could have no relevance to urinary As in the populations studied [ 108 , 109 ]. while in other studies individuals who were GSTT1 null had an elevated DMA% in urine [ 110 ], a higher proportion of MMA, a significantly higher PMI and a significantly lower SMI [ 60 , 111 ]. Our results do not confirm previous findings and although GSTT1 could be involved in As metabolism and influence the internal dose of methylated As, its role remains to be fully elucidated.…”

Section: Discussionmentioning

confidence: 95%

“…Growing interest has recently focused on the factors influencing As methylation. Besides the As exposure, individual’s ethnicity [ 17 ], age, gender, Body Mass Index (BMI) [ 34 , 47 , 53 ], tobacco smoking [ 54 ], dietary habits [ 55 , 56 ], and inherited genetic characteristics [ 57 , 58 , 59 , 60 , 61 ] were reported to be related to MC.…”

Section: Introductionmentioning

confidence: 99%

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Factors Affecting Arsenic Methylation in Contaminated Italian Areas

Bustaffa

Gorini

Bianchi

et al. 2020

IJERPH

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Chronic arsenic (As) exposure is a critical public health issue. The As metabolism can be influenced by many factors. The objective of this study is to verify if these factors influence As metabolism in four Italian areas affected by As pollution. Descriptive analyses were conducted on 271 subjects aged 20–49 in order to assess the effect of each factor considered on As methylation. Percentages of metabolites of As in urine, primary and secondary methylation indexes were calculated as indicators for metabolic capacity. The results indicate that women have a better methylation capacity (MC) than men, and drinking As-contaminated water from public aqueducts is associated with poorer MC, especially in areas with natural As pollution. In areas with anthropogenic As pollution occupational exposure is associated with a higher MC while smoking with a poorer MC. Dietary habits and genetic characteristics are probably implicated in As metabolism. BMI, alcohol consumption and polymorphism of the AS3MT gene seem not to influence As MC. Arsenic metabolism may be affected by various factors and in order to achieve a comprehensive risk assessment of As-associated disease, it is crucial to understand how these factors contribute to differences in As metabolism.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

Factors Affecting Arsenic Methylation in Contaminated Italian Areas

Bustaffa

Gorini

Bianchi

et al. 2020

IJERPH

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“…Its reduced state can donate a reducing equivalent to other molecules, and be involved in the reducing reactions of arsenic methylation ( Kobayashi et al, 2005 ; Waters et al, 2004 ). There is debate on whether SNPs in the GST family are associated with arsenic methylation efficiency ( Kile et al, 2005 ; McCarty et al, 2007 ; Steinmaus et al, 2007 ; Yang et al, 2015 ). One study found that SNPs in GSTT1 and GSTM1 are associated with MMA and DMA levels ( Yang et al, 2015 ), while another study's findings did not support this conclusion ( Kile et al, 2013 ).…”

Section: Discussionmentioning

confidence: 99%

“…There is debate on whether SNPs in the GST family are associated with arsenic methylation efficiency ( Kile et al, 2005 ; McCarty et al, 2007 ; Steinmaus et al, 2007 ; Yang et al, 2015 ). One study found that SNPs in GSTT1 and GSTM1 are associated with MMA and DMA levels ( Yang et al, 2015 ), while another study's findings did not support this conclusion ( Kile et al, 2013 ). There is also no agreement about the SNP-environment interactions of these genes.…”

Section: Discussionmentioning

confidence: 99%

Gene-environment interaction and maternal arsenic methylation efficiency during pregnancy

Gao

Mostofa

Quamruzzaman

et al. 2019

Environment International

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Background: Single nucleotide polymorphisms (SNPs) may influence arsenic methylation efficiency, affecting arsenic metabolism. Whether gene-environment interactions affect arsenic metabolism during pregnancy remains unclear, which may have implications for pregnancy outcomes. Objective: We aimed to investigate main effects as well as potential SNP-arsenic interactions on arsenic methylation efficiency in pregnant women. Method: We recruited 1613 pregnant women in Bangladesh, and collected two urine samples from each participant, one at 4–16 weeks, and the second at 21–37 weeks of pregnancy. We determined the proportions of each arsenic metabolite [inorganic As (iAs)%, monomethylarsonic acid (MMA)%, and dimethylarsinic acid (DMA)%] from the total urinary arsenic level of each sample. A panel of 63 candidate SNPs was selected for genotyping based on their reported associations with arsenic metabolism (including in As3MT, N6AMT1, and GST02 genes). We used linear regression models to assess the association between each SNP and DMA% with an additive allelic assumption, as well as SNP-arsenic interaction on DMA%. These analyses were performed separately for two urine collection time-points to capture differences in susceptibility to arsenic toxicity. Result: Intron variants for As3MT were associated with DMA%. rs9527 (β = − 2.98%, P FDR = 0.008) and rs1046778 (β = 1.64%, P FDR = 0.008) were associated with this measure in the early gestational period; rs3740393 (β = 2.54%, P FDR = 0.002) and rs1046778 (β = 1.97%, P FDR = 0.003) in the mid-to-late gestational period. Further, As3MT, GSTO2, and N6AMT1 polymorphisms showed different effect sizes on DMA% conditional on arsenic exposure levels. However, SNP-arsenic interactions were not statistically significant after adjusting for false discovery rate (FDR), rs1048546 in N6AMT1 had the highest significance level in the SNP-arsenic interaction test during mid-to-late gestation (β = −1.8% vs. 1.4%, P GXE_FDR = 0.075). Finally, As3MT and As3MT/CNNM2 haplotypes were associated with DMA% at both time points. Conclusion: We found that not all genetic associations reported in arsenic methylation efficiency replicate in pregnant women. Arsenic exposure level has a limited effect in modifying the association between genetic variation and arsenic methylation efficiency.

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“…Majority of the researchers found that people with skin lesions and high arsenic exposure are likely to have reduced arsenic methylation capacity with high trivalent species MMA in urine ( 45 – 48 ). The methylation capacity might reduce with increasing dose of arsenic, smoking and alcohol consumption, age, and nutritional folate deficiency ( 46 , 49 , 50 ). On the contrary, one study from China reported about higher methylation capacity among people above 40 years of age compared to below 40 years, but they also found positive correlation between %MMA and risk of skin lesion.…”

Section: Understanding the Present State Of Researchmentioning

confidence: 99%

Recent Advances in Arsenic Research: Significance of Differential Susceptibility and Sustainable Strategies for Mitigation

Sanyal

Bhattacharjee

Paul

2020

Front. Public Health

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Arsenic contamination in drinking water and associated adverse outcomes are one of the major health issues in more than 50 countries worldwide. The scenario is getting even more detrimental with increasing number of affected people and newer sites reported from all over the world. Apart from drinking water, the presence of arsenic has been found in various other dietary sources. Chronic arsenic toxicity affects multiple physiological systems and may cause malignancies leading to death. Exposed individuals, residing in the same area, developed differential dermatological lesion phenotypes and varied susceptibility toward various other arsenic-induced disease risk, even after consuming equivalent amount of arsenic from the similar source, over the same duration of time. Researches so far indicate that differential susceptibility plays an important role in arsenic-induced disease manifestation. In this comprehensive review, we have identified major population-based studies of the last 20 years, indicating possible causes of differential susceptibility emphasizing arsenic methylation capacity, variation in host genome (single nucleotide polymorphism), and individual epigenetic pattern (DNA methylation, histone modification, and miRNA expression). Holistic multidisciplinary strategies need to be implemented with few sustainable yet cost-effective solutions like alternative water source, treatment of arsenic-contaminated water, new adaptations in irrigation system, simple modifications in cooking strategy, and dietary supplementations to combat this menace. Our review focuses on the present perspectives of arsenic research with special emphasis on the probable causes of differential susceptibility toward chronic arsenic toxicity and sustainable remediation strategies.

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Associations between the polymorphisms of GSTT1, GSTM1 and methylation of arsenic in the residents exposed to low-level arsenic in drinking water in China

Cited by 7 publications

References 23 publications

Factors Affecting Arsenic Methylation in Contaminated Italian Areas

Factors Affecting Arsenic Methylation in Contaminated Italian Areas

Gene-environment interaction and maternal arsenic methylation efficiency during pregnancy

Recent Advances in Arsenic Research: Significance of Differential Susceptibility and Sustainable Strategies for Mitigation

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