Article

GSTO and AS3MT genetic polymorphisms and differences in urinary arsenic concentrations among residents in Bangladesh

Department of Environmental Health, Harvard School of Public Health, Boston, MA 02115, USA.
Biomarkers (Impact Factor: 2.52). 02/2012; 17(3):240-7. DOI: 10.3109/1354750X.2012.658863
Source: PubMed

ABSTRACT We determined whether single nucleotide polymorphisms (SNPs) in the glutathione S-transferase omega (GSTO) and arsenic(III)methyltransferase (AS3MT) genes were associated with concentrations of urinary arsenic metabolites among 900 individuals without skin lesions in Bangladesh. Four SNPs were assessed in these genes. A pathway analysis evaluated the association between urinary arsenic metabolites and SNPs. GSTO1 rs4925 homozygous wild type was significantly associated with higher monomethylarsonic acid (MMA) and dimethylarsinic acid urinary concentrations, whereas wild-type AS3MT rs11191439 had significantly lower levels of As(III) and MMA. Genetic polymorphisms GSTO and As3MT modify arsenic metabolism as evidenced by altered urinary arsenic excretion.

Download full-text

Full-text

Available from: Elaine Borland Hoffman, PhD, Aug 17, 2015
1 Follower
 · 
126 Views
  • Source
    • "Key enzymes involved in the onecarbon methylation of As with S-adenosyl methionine (SAM) as the methyl donor include arsenic-3-methyltransferase (AS3MT), methylenetetrahydrofolate reductase (MTHFR), cystathionine beta-synthase (CBS), and purine nucleoside phosphorylase (PNP). Genetic polymorphisms in genes encoding the above-mentioned enzymes have been related to differences in the distribution of As metabolites in urine (Agusa et al., 2010; Engstrom et al., 2011; Lindberg et al., 2007; Marnell et al., 2003; Pierce et al., 2012; Porter et al., 2010; Rodrigues et al., 2012; Schlawicke Engstrom et al., 2007; Steinmaus et al., 2007; Yu et al., 2003). Some of these polymorphisms have also been related to CVD risk (Agusa et al., 2010; de Waart et al., 2001; Klerk et al., 2002; Kolsch et al., 2004, 2007; Li et al., 2001; Olshan et al., 2003; Pezzini et al., 2002; Roest et al., 2001; Wang et al., 2002). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Epidemiologic studies that evaluated genetic susceptibility to the effects of arsenic exposure from drinking water on subclinical atherosclerosis are limited. We conducted a cross-sectional study of 1,078 participants randomly selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh to evaluate whether the association between arsenic exposure and carotid artery intima-medial thickness (cIMT) differs by 207 single-nucleotide polymorphisms (SNPs) in 18 genes related to arsenic metabolism, oxidative stress, inflammation, and endothelial dysfunction. Although not statistically significant after correcting for multiple testing, nine SNPs in APOE, AS3MT, PNP, and TNF genes had a nominally statistically significant interaction with well-water arsenic in cIMT. For instance, the joint presence of a higher level of well-water arsenic (≥ 40.4 μg/L) and the GG genotype of AS3MT rs3740392 was associated with a difference of 40.9 μm (95% CI=14.4, 67.5) in cIMT, much greater than the difference of cIMT associated with the genotype alone (β=-5.1 μm, 95% CI=-31.6, 21.3) or arsenic exposure alone (β=7.2 μm, 95% CI=-3.1, 17.5). The pattern and magnitude of the interactions were similar when urinary arsenic was used as the exposure variable. Additionally, the at-risk genotypes of the AS3MT SNPs were positively related to proportion of monomethylarsonic acid (MMA) in urine, which is indicative of arsenic methylation capacity. The findings provide novel evidence that genetic variants related to arsenic metabolism may play an important role in arsenic-induced subclinical atherosclerosis. Future replication studies in diverse populations are needed to confirm the findings.
    Toxicology and Applied Pharmacology 03/2014; 276(3). DOI:10.1016/j.taap.2014.02.014 · 3.63 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Potential occupational arsenic exposure is a significant problem in smelting plants. The metabolites containing arsenic with an oxidation of +3 have been considered more cytotoxic and genotoxic than their parent inorganic species. The current study examined the capacity of arsenic methylation and its risk on skin lesions. The primary aim of this study is to determine if methylation capacity, as measured by urinary arsenic metabolites, differed in workers with skin lesions compared to workers without skin lesions. Hydride generation-atomic absorption spectrometry was used to determine three arsenic species in urine of workers who had been working in arsenic plants, and primary and secondary methylation indexes were calculated. Skin lesions were examined at the same time. Many workers had obvious skin lesions (36/91). The mean concentrations of inorganic arsenic (iAs), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA) in urine of workers are obviously higher than those of the control group. There are more iAs, MMA, and DMA in urine, higher MMA%, lower iAs% for workers with skin lesions compared with those without skin lesions. Workers with skin lesions have the lowest SMI (3.50±1.21), and they may be in danger. Our results support the viewpoint that individuals who metabolize inorganic arsenic to MMA easily, but metabolize MMA to DMA difficulty have more risk of skin lesions.
    07/2012; 34(2):624-630. DOI:10.1016/j.etap.2012.07.003
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A repeated measures study was conducted in Pabna, Bangladesh to investigate factors that influence biomarkers of arsenic exposure. Drinking water arsenic concentrations were measured by inductively-coupled plasma mass spectrometry (ICP-MS) and urinary arsenic species [arsenite (As3), arsenate (As5), monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA)] were detected using High Performance Liquid Chromatography (HPLC) and Hydride Generated Atomic Absorption Spectrometry (HGAAS). Linear mixed effects models with random intercepts were used to evaluate the effects of arsenic contaminated drinking water, genetic polymorphisms in glutathione-S-transferase (GSTT1 and GSTM1) on total urinary arsenic, primary methylation index [MMA/(As3+As5)], secondary methylation index (DMA/MMA), and total methylation index [(MMA+DMA)/(As3+As5)]. Drinking water arsenic concentrations were positively associated with total urinary arsenic concentrations and total methylation index. A significant gene-environment interaction was observed between urinary arsenic exposure in drinking water GSTT1 but not GSTM1 where GSTT1 null individuals had a slightly higher excretion rate of arsenic compared to GSTT1 wildtypes after adjusting for other factors. Additionally, individuals with GSTT1 null genotypes had a higher primary methylation index and lower secondary methylation index compared to GSTT1 wildtype after adjusting for other factors. This data suggests that GSTT1 contributes to the observed variability in arsenic metabolism. Since individuals with a higher primary methylation index and lower secondary methylation index are more susceptible to arsenic related disease, these results suggest that GSTT1 null individuals may be more susceptible to arsenic-related toxicity. No significant associations were observed between GSTM1 and any of the arsenic methylation indices.
    Journal of Indian Society of Periodontology 05/2013; 67(2):197-207.
Show more