Arsenic (+3 Oxidation State) Methyltransferase Proteins (AS3MT)

Human Arsenic (+3 Oxidation State) Methyltransferase (AS3MT) interaction partners

1. The median concentration of arsenic in water was 82 mug/L; the levels of urinary excretion of dimethylarsinic acid (DMA) were higher in women than in the men. The carriers of the CC genetic variant of the As3MT (rs3740393) gene showed higher urinary concentrations of methylarsinic acid (p=0.01) and DMA (p=0.05)

2. combined effect of N6AMT1 haplotype 2_GGCCAT and As3MT haplotype 2_GCAC showed consistence with the additive significance of each haplotype on % iAs: the mean was 5.47% and 9.36% for carriers with both and null haplotypes, respectively

3. Maternal alleles for five of the seven SNPs (rs7085104, rs3740400, rs3740393, rs3740390, and rs1046778) were associated with urinary concentrations of iAs metabolites, and alleles for one SNP (rs3740393) were associated with birth outcomes/measures. These associations were strongly dependent upon the male sex of the fetus but independent of fetal genotype for AS3MT.

4. In this large-scale, Han Chinese population-based genetic association study for genetic susceptibility to schizophrenia of a three-gene cluster region, AS3MT-CNNM2-NT5C2, two SNPs with independent effects, rs11191419 and rs11191514, were identified. Rs11191419 is located on the 5' (potential promoter) region of AS3MT, while rs11191514 is located in one of the introns of CNNM2.

5. The combined analysis confirmed evidence of genome-wide significant associations in the Han Chinese population for three loci, at 2p16.1 (rs1051061, in an exon of VRK2, P=1.14 x 10-12, odds ratio (OR)=1.17), 6p22.1 (rs115070292 in an intron of GABBR1, P=4.96 x 10-10, OR=0.77) and 10q24.32 (rs10883795 in an intron of AS3MT, P=7.94 x 10-10, OR=0.87; rs10883765 at an intron of ARL3, P=3.06 x 10-9, OR=0.87).

6. this study implicates altered neural expression of BORCS7, AS3MT, and NT5C2 in susceptibility to schizophrenia arising from genetic variation at the chromosome 10q24 locus

7. AS3MT and N6AMT1 polymorphisms and urinary arsenic metabolites (%iAs, %MMA, %DMA) in 722 subjects from an arsenic-cancer case-control study in a uniquely exposed area in northern Chile, were examined.

8. Risk alleles spanning multiple genes across the 10q24.32 schizophrenia-related locus are associated in the human brain selectively with an increase in the expression of both BLOC-1 related complex subunit 7 (BORCS7) and a previously uncharacterized, human-specific arsenite methyltransferase (AS3MT) isoform (AS3MTd2d3).

9. A joint dose-response effect was identified for a AS3MT high-risk haplotype and inefficient arsenic methylation capacity on developmental delay.

10. genome-wide association study in population in United States (AZ, OK, SD, ND): Data suggest SNPs in AS3MT (rs17878846, rs10509760) partly explain inter-individual variability in susceptibility to arsenic poisoning (and urine arsenic species patterns).

11. Its genotype-dependent differences in arsenic metabolism is noted.(review)

12. The present study found that rs3740400 in As3MT and rs156697 in GSTO2 were strongly associated with the arsenic species (%iAs, %MMA and MMA/iAs and DMA/MMA ratios) in urine of the occupationally exposed workers and they may influence methylation capacity.

13. analysis of the functional roles of GSH and the crucial Cys residues in iAs3+ methylation catalyzed by hAS3MT

14. a strong signal of positive selection in the main arsenic methyltransferase AS3MT gene, which has been previously associated with lower concentrations of the most toxic product of arsenic metabolism monomethylarsonic acid.

15. This study's results provide preliminary evidence for the over-transmission of the A allele at the AS3MT rs11191454 polymorphism in Attention Deficit Hyperactivity Disorder.

16. Influence of the level of arsenic exposure and the presence of T860C polymorphism in human As urinary metabolic profile

17. Functions of arsenic (III) methyltransferase S-adenosylmethionine binding site were evaluated.

18. Genetic variation in AS3MT gene is associated with arsenic metabolism and risk of basal cell carcinoma.

19. Two SNPs, AS3MT 12390 (rs3740393) and 14458 (rs11191439) were consistently related to arsenic methylation regardless of the populations examined for the analysis.

20. AS3MT SNPs were associated with arsenic metabolism efficiency and arsenic toxicity in exposed individuals.

Mouse (Murine) Arsenic (+3 Oxidation State) Methyltransferase (AS3MT) interaction partners

1. As3mt role in obesity and insulin resistance

2. Data, including date from studies in knockout mice, suggest that As3mt is involved in energy metabolism in a sex-specific manner, independent of inorganic arsenic poisoning; thus, As3mt may be involved in cellular processes beyond methylation of inorganic arsenic.

3. Oxidative damage and Ogg1 deficient background exacerbate repair deficiencies.. Overexpression of the arsenic metabolizing enzyme As3mt acts as adaptive mechanism.

4. Simple hyperplasia of the bladder epithelium was detected in all As3mt KO mice treated with sodium arsenite.

5. Rat, mouse and human are efficient methylators of inorganic arsenic. Findings suggest a role for AS3MT in the methylation of inorganic arsenic.