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IFNL1 gene promoter single nucleotide polymorphism rs7247086 enhances transcription through a STAT-binding site.

Created on 17 Aug 2026

Authors

Sapana Kaushik, Seema Bharatiya, Debarati Guha Roy, Darshan Panchariya, Ahona Roy, Dhara Raval, Avik Mondal, Aparna Palit, Sreedhar Chinnaswamy

Published in

Cytokine. Volume 207. Pages 157200. Aug 16, 2026. Epub Aug 16, 2026.

Abstract

A single nucleotide polymorphism (SNP) within the human interferon lambda 1 (IFN-L1, IFN-λ1) gene promoter, rs7247086 (C/T) has been reported to be associated with severe dengue and possibly with psoriasis and COVID-19. However, its functional nature is unknown. The present study was undertaken to examine the effect of rs7247086 on transcription, by utilizing promoter and enhancer-reporter assays. We see that the T allele completes a consensus signal transducer and activator of transcription (STAT)-binding site. While we did not find strong evidence to show that the STAT-binding site drove transcription from the IFNL1 gene promoter, we saw that it acts like an enhancer in reporter assays. The T allele of rs7247086 within the STAT-binding site significantly increased transcription of the reporter gene compared to the C allele when incorporated into enhancer-reporter constructs in both HEK293 and A549 cell lines. Mechanistically, we obtained evidence from electrophoretic mobility shift assays to show that the T allele binds to STAT proteins more strongly than the C allele. In a cohort of healthy individuals, we saw that the T allele carriers, specifically males but not females, had significantly increased secretion of IFN-λ1 from their peripheral blood mononuclear cells after stimulation. Lastly, rs7247086 significantly associated with psoriasis, only in males but not in females.

PMID:
42604633
Bibliographic data and abstract were imported from PubMed on 17 Aug 2026.

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