Genetic susceptibility to adverse arsenic-related cardiometabolic outcomes: a systematic review

Millions of people worldwide are chronically exposed to environmental arsenic through drinking water, increasing their risk of various adverse cardiometabolic outcomes. To understand the inter-individual variation in arsenic susceptibility, this systematic review explores all epidemiological evidence on interactions between single nucleotide polymorphisms (SNPs) and arsenic exposure in relation to cardiometabolic health. Five electronic databases were searched until April 2023. From 42,202 retrieved publications, 18 candidate gene-environment (cGxE) studies were included, and no genome-wide association studies were found. Of 676 SNPs in 148 genes tested, 40 SNPs in 24 genes, 4 haplotypes and combined SNPs in MCP-1/APOE, were reported to statistically significantly interact with arsenic exposure. These genes were involved in arsenic metabolism, oxidative stress or defence, DNA damage repair, endothelial (dys) function, inflammation or immune function, tumour suppressor activity, or were previously implicated in cardiometabolic disease pathways. Most studies did not explore the same SNPs (or strong proxies), and none of the identified SNP-arsenic interactions were replicated for the same arsenic species and cardiometabolic outcome. Whilst some SNPs are suggestive of influencing susceptibility to arsenic for various cardiometabolic outcomes, further research is needed to understand the interplay between arsenic and genetic variants, identify at-risk populations, and improve risk assessment.