# Arsenic and the Human Genome:  susceptibility and response to exposure Supplement 4

> **NIH NIH R35** · UNIVERSITY OF CHICAGO · 2024 · $66,891

## Abstract

ABSTRACT
Chronic exposure to inorganic arsenic is a global public health concern affecting over 100 million
people worldwide. Arguably the largest poisoned population in history, more than 57 million people in
Bangladesh are persistently exposed to arsenic by consuming contaminated water. The toxic effects
of exposure to arsenic-contaminated drinking water include numerous cancers and non-malignant
morbidities; however, variability in the presentation and severity of arsenic-induced diseases exists.
Inherited variation has been implicated in susceptibility to arsenic toxicity and the biological response
to arsenic exposure. Therefore, efforts to identify genetic determinants of arsenic metabolism
efficiency (AME), a key regulator of toxicity risk and outcomes, and susceptibility to arsenic toxicity
have been made in the field of genetic epidemiology. Although previous studies identified loci and
genetic variants associated with risk of AME and dermatological outcomes, none of these studies
focused exclusively on identifying single nucleotide polymorphisms (SNPs) in non-coding RNA
regions of the genome associated with the aforementioned traits. For this reason, the main objective
of the proposed research is to identify functional variants in non-coding RNA genes associated with
susceptibility to arsenic toxicity and characterize their potential functional effects. The aims include
identifying SNPs in microRNA-encoding sequences and 3’UTR sequences of messenger RNAs that
disrupt microRNA-mRNA interactions, and that are associated with arsenic-induced skin lesion
development. Our research strategy includes leveraging existing data from the The Health Effects of
Arsenic Longitudinal Study cohort, a group of >8,000 Bangladeshi participants with varying levels of
exposure to arsenic-contaminated drinking water. The proposed project will advance our
understanding of genetic and environmental susceptibility to dermatological diseases, identify
potential therapeutic gene and pathway targets to treat arsenic toxicity, provide insights about
processes likely involved in the etiology of arsenic-induced diseases, and inform potential prevention
strategies. The goal of the training plan described in the proposal will cultivate expertise in molecular
and genetic epidemiology, and environmental health research, while preparing the trainee for an
academic research career focused on contributing meaningful knowledge regarding the understudied
focus on variants in functional, non-coding elements of the genome.

## Key facts

- **NIH application ID:** 10938639
- **Project number:** 3R35ES028379-07S2
- **Recipient organization:** UNIVERSITY OF CHICAGO
- **Principal Investigator:** Brandon Lee Pierce
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $66,891
- **Award type:** 3
- **Project period:** 2017-09-15 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10938639

## Citation

> US National Institutes of Health, RePORTER application 10938639, Arsenic and the Human Genome:  susceptibility and response to exposure Supplement 4 (3R35ES028379-07S2). Retrieved via AI Analytics 2026-07-26 from https://api.ai-analytics.org/grant/nih/10938639. Licensed CC0.

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