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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\u2019s 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.<\/jats:p>","DOI":"10.3390\/ijms26188806","type":"journal-article","created":{"date-parts":[[2025,9,10]],"date-time":"2025-09-10T12:04:55Z","timestamp":1757505895000},"page":"8806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Functional Role of Single-Nucleotide Polymorphisms on IFNG and IFNGR1 in Humans with Cardiovascular Disease"],"prefix":"10.3390","volume":"26","author":[{"given":"Megh","family":"Mehta","sequence":"first","affiliation":[{"name":"Immunology Center of Georgia, Augusta University, Augusta, GA 30912, USA"},{"name":"Medical College of Georgia, Augusta University, Augusta, GA 30909, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of 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