# Functional Role of Single-Nucleotide Polymorphisms on IFNG and IFNGR1 in Humans with Cardiovascular Disease

## TL;DR

This study explores how genetic variations affect immune cell gene expression in people with HIV and cardiovascular disease.

## Contribution

The study identifies specific SNPs that influence IFNG and IFNGR1 expression in immune cells linked to cardiovascular disease.

## Key findings

- 187 significant sc-eQTLs were identified, with 160 specific to one immune cell type.
- Three sc-eQTLs affect IFNGR1 expression in CD4+ T cells at both mRNA and protein levels.
- Two sc-eQTLs impact IFNG expression in CD8+ T cells and are linked to Th1 gene patterns.

## Abstract

HIV infection is known to increase the risk for cardiovascular disease (CVD). Although almost 400 single-nucleotide polymorphisms (SNPs) are significantly associated with CAD alone, a subtype of CVD, the functions of most of these risk loci are unclear. Here, we investigated the impact of genetic variants/SNPs on the expression of nearby genes as potential cis expression quantitative trait loci (cis-eQTLs). We investigated peripheral blood mononuclear cells (PBMCs) from 31 participants in the Women’s Interagency HIV Study (WIHS) using genotyping, single-cell (sc)RNA-seq, and CITE-seq. We found 187 statistically significant sc-eQTLs (single-cell eQTLs). In total, 160 were specific for just one immune cell type. We found a set of 3 sc-eQTLs impacting expression of IFNGR1 in CD4+ T cells at the mRNA and protein level as detected by flow cytometry. Two other sc-eQTLs representing one locus impact IFNG expression in CD8+ T cells, one of the primary sources of this cytokine. The sc-eQTLs impacting IFNG were associated with Th1 (T-helper1) gene expression patterns in CD4+ T cells in this cohort. These data suggest that some individuals are genetically predisposed to greater levels of Th1 polarization, which is known to be associated with atherosclerosis.