# Role of African-centric TP53 variant in higher H. pylori prevalence in African Americans

> **NIH NIH R01** · WISTAR INSTITUTE · 2021 · $636,016

## Abstract

Project Summary
African Americans have a 6-fold higher H. pylori (Hp) infection than the non-Hispanic white population; however,
underlying gene(s) for this disparity remain elusive. We discovered that a human TP53 gene variant at amino
acid 47 exists predominantly in people of African descent. Macrophages containing the S47 variant are defective
in ferroptosis, M2 polarized and show more productive infections by Hp and other bacteria. Macrophage adaptive
response is essential for eliminating Hp infection and is suppressed in chronic infections that lead to gastritis.
Our collaborator, Dr. Keith Wilson, reported the role of Arg2 activation by Hp in suppressing the macrophage
response. Unbiased WT and S47 macrophage proteomics revealed marked differences in Liver X Receptor
activation, arginase II activity, inflammation, iron transport and antibacterial defense machinery which regulate
immune response and directly affect outcomes of bacterial infections. Although p53 is known to regulate immune
response, we are the first to discover the exact genetic variant causing the disparities. We will reverse the Hp
infection disparities in African Americans with the S47 SNP by in-depth mechanistic and therapeutic study.
Our human studies will give translational relevance to this project. We will test ~500 Hp seropositive African
American samples for the prevalence of S47 and other SNPs. Then we will focus on improving macrophage
response, Hp clearance and reduce chronic gastric dysplasia in S47 mice using Liver X Receptor (LXR) agonists.
We will test if LXR activation improves these outcomes for multiple Hp strains with differing virulence. Moreover,
we will generate a genome-wide map of macrophage binding of LXR to ‘fine tune’ its activity on macrophage
activation and eliminate undesired effect of hepatic steatosis.
Since Hp is found both extracellularly and within macrophages, specific depletion of immune cells will be
used to distinguish the role of macrophages from other tissue environment in H. pylori pathogenesis. These
studies will be validated by bone marrow swaps between WT and S47 mice. we will test macrophage
regulation and tissue environment for more. We will prioritize and test pathways associated with LXR such
as arginase pathway (Arg2, Slc7a2), iron transport (Tfrc, Slc40a1, Fth1) and innate immune proteins (TLR3 and
TLR7) as novel therapeutic targets. Lastly, we will test macrophage regulatory factors (NOTCH1 and
mTOR), energy metabolism (switching from ox-phos to glycolysis by Metformin) and polyamine pathway
(DFMO-polyamine synthesis inhibitor) in fine tuning LXR agonist induced reversal of anti-inflammatory
polarization in S47 mice, clearance of Hp infection and reduction of gastric dysplasia.
This proposal will a) improve our understanding of the biological mechanism for the disparity in Hp infection in
African Americans and b) provide several therapeutic avenues to improve clearance of Hp infection and gastritis.
This project is a stepp...

## Key facts

- **NIH application ID:** 10119864
- **Project number:** 1R01DK124385-01A1
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Daniel Thomas Claiborne
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $636,016
- **Award type:** 1
- **Project period:** 2021-01-20 → 2025-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10119864

## Citation

> US National Institutes of Health, RePORTER application 10119864, Role of African-centric TP53 variant in higher H. pylori prevalence in African Americans (1R01DK124385-01A1). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10119864. Licensed CC0.

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