{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T06:33:44Z","timestamp":1767335624104,"version":"3.48.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T00:00:00Z","timestamp":1767312000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"\n Background<\/jats:title>\n \n The Fc receptor-like protein 3 (\n FCRL3<\/jats:italic>\n ) gene encodes a transmembrane receptor that is predominantly expressed on the surfaces of regulatory T cells (Tregs). The single-nucleotide polymorphism (SNP) rs7528684 (\u2212169T\/C) in the\n FCRL3<\/jats:italic>\n gene has been hypothesised to enhance its expression, which in turn causes dysfunction of Tregs and results in loss of self-tolerance as well as diminished production of anti-inflammatory cytokines. This process triggers rapid proliferation of the autoreactive T cells and other immune cells, exacerbating the progression of rheumatoid arthritis (RA) and other autoimmune diseases.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n In the current study, we screened the\n FCRL3<\/jats:italic>\n SNP rs7528684 to assess its association with the risk of RA in the Indian population. The screening was performed using high-resolution melting analysis, and the findings were confirmed via Sanger sequencing. We further analysed the impacts of rs7528684 on\n FCRL3<\/jats:italic>\n , forkhead box protein 3 (\n FOXP3),<\/jats:italic>\n and interleukin-35 (\n IL-35<\/jats:italic>\n ) gene expressions using quantitative real-time polymerase chain reaction. The gene expression correlation between\n FCRL3<\/jats:italic>\n and\n FOXP3<\/jats:italic>\n mRNA expression was analysed using Spearman\u2019s rank correlation coefficient (\u03c1) analysis. Concurrently, the inflammatory serological biomarkers immunoglobulin G rheumatoid factor (IgG-RF) and C-reactive protein were evaluated in the RA patients.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The\n FCRL3<\/jats:italic>\n SNP rs7528684 C\/C genotype was significantly associated with increased risk of RA in the Indian ethnicity (\n p =<\/jats:italic>\n 0.0005)\n .<\/jats:italic>\n Furthermore, the C allele frequency was significantly elevated within the RA group (58.6%). Similarly, RA patients carrying the C\/C genotype also exhibited higher\n FCRL3<\/jats:italic>\n mRNA expression levels than the controls (\n p =<\/jats:italic>\n 0.0072). Additionally,\n FOXP3<\/jats:italic>\n and\n IL-35<\/jats:italic>\n mRNA expressions were downregulated in RA patients carrying the C\/C genotype. The\n FCRL3<\/jats:italic>\n mRNA expression demonstrated a significant negative correlation with\n FOXP3<\/jats:italic>\n mRNA expression (\u03c1 = - 0.5526,\n p<\/jats:italic>\n = 0.0094, R\n 2<\/jats:sup>\n = 0.3052) in RA patients. The results also showed positive correlations between the C\/C genotype and IgG-RF-positive RA cases.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Our findings validate that the C\/C genotype of the\n FCRL3<\/jats:italic>\n SNP rs7528684 is strongly associated with RA in the Indian ethnicity. This genotype is characterised by positive IgG-RF and upregulated\n FCRL3<\/jats:italic>\n and downregulated\n FOXP3<\/jats:italic>\n and\n IL-35<\/jats:italic>\n as key anti-inflammatory cytokines. Concurrently,\n FCRL3<\/jats:italic>\n and\n FOXP3<\/jats:italic>\n mRNA expression levels are inversely correlated.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fgene.2025.1720056","type":"journal-article","created":{"date-parts":[[2026,1,2]],"date-time":"2026-01-02T06:29:15Z","timestamp":1767335355000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Impacts of rs7528684 (\u2212169T\/C) on FCRL3, FOXP3, and IL-35 gene expressions and IgG-RF correlation: insights into the pathogenesis of rheumatoid arthritis"],"prefix":"10.3389","volume":"16","author":[{"given":"S.","family":"Mohamed Muzammil","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"S.","family":"Asha Devi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1292","DOI":"10.1016\/j.celrep.2019.12.099","article-title":"Human Fc receptor-like 3 inhibits regulatory T cell function and binds secretory IgA","volume":"30","author":"Agarwal","year":"2020","journal-title":"Cell Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1111\/cei.13290","article-title":"Mechanisms of human FoxP3+ Treg cell development and function in health and disease","volume":"197","author":"Attias","year":"2019","journal-title":"Clin. 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