Determinants and Consequences of Arsenic Metabolism Efficiency among 4,794 Individuals: Demographics, Lifestyle, Genetics, and Toxicity

Abstract

Background Exposure to inorganic arsenic (iAs), class I carcinogen, affects several hundred-million people worldwide. Once absorbed, iAs is converted to monomethylated (MMA) and then dimethylated forms (DMA), with methylation facilitating urinary excretion. The abundance of each species in urine relative to their sum (iAs%, MMA%, and DMA%), varies across individuals, reflecting differences in arsenic metabolism capacity. Methods The association of arsenic metabolism phenotypes with participant characteristics and arsenical skin lesions was characterized among 4,794 participants in the Health Effects of Arsenic Longitudinal Study (Araihazar, Bangladesh). Metabolism phenotypes include those obtained from principal components (PC) analysis of arsenic species. Results Two independent PCs were identified: PC1 appears to represent capacity to produce DMA (2nd methylation step), and PC2 appears to represent capacity to convert iAs to MMA (1st methylation step). PC 1 was positively associated (p <0.05) with age, female sex, and BMI, while negatively associated with smoking, arsenic exposure, education, and land ownership. PC2 was positively associated with age and education but negative associated with female sex and BMI. PC2 was positively associated with skin lesion status, while PC1 was not. 10q24.32/AS3MT region polymorphisms were strongly associated with PC1, but not PC2. Patterns of association for most variables were similar for PC1 and DMA%, and for PC2 and MMA% with the exception of arsenic exposure and SNP associations. Conclusions Two distinct arsenic metabolism phenotypes show unique associations with age, sex, BMI, 10q24.32 polymorphisms, and skin lesions. Impact: This work enhances our understanding of arsenic metabolism kinetics and toxicity risk profiles.

The Association of Arsenic Metabolism with Cancer, Cardiovascular Disease, and Diabetes: A Systematic Review of the Epidemiological Evidence

“…Beyond arsenic exposure levels, genetic polymorphisms, particularly in the arsenic (III) methyltransferase (AS3MT) gene, have been considered major determinants in interindividual variability of the arsenic methylation patterns ( Agusa et al 2011 ; Eichstaedt et al 2015 ). Age, sex, and body mass index may be other major determinants of arsenic metabolism ( Jansen et al 2015 ). Epidemiological studies of arsenic metabolism and disease need to carefully consider for which factors to adjust.…”

Concentrations of urinary arsenic species in relation to rice and seafood consumption among children living in Spain

“…The relative proportion of urinary arsenic species is a widely used measure of an individual’s i-As methylation capacity, which is determined at least in part by genetic factors such as polymorphisms in the arsenic methyltransferase (AS3MT) gene (Jansen et al, 2016; Skröder Löveborn et al, 2016; Tseng, 2009). Children’s ability to methylate i-As has been reported to be more efficient than their mothers (Skröder Löveborn et al, 2016).…”

Arsenic metabolism and one-carbon metabolism at low-moderate arsenic exposure: Evidence from the Strong Heart Study

“…(Chen et al 2012; Del Razo et al 2011; Kuo et al 2015; Mendez et al 2016; Nizam et al 2013; Wang et al 2007) Understanding non-modifiable (genetics, sex, life-stage) and modifiable (smoking, alcohol intake, kidney function, body mass index, nutrition) determinants of arsenic metabolism is important given the role of arsenic metabolism in arsenic toxicity. (Balakrishnan et al 2016; Council 2013; Gribble et al 2013; Jansen et al 2016)…”