| Title: | IFNL4 genotype is associated with hepatitis A virus infection findings from a focused phenotype study in the UK Biobank Cohort |
| Journal: | International Journal of Infectious Diseases |
| Published: | 14 Feb 2026 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/41698497/ |
| DOI: | https://doi.org/10.1016/j.ijid.2026.108483 |
| URL: | https://www.ijidonline.com/article/S1201-9712(26)00118-9/pdf |
Publication 17761
WARNING: the interactive features of this website use CSS3, which your browser does not support. To use the full features of this website, please update your browser.
Abstract
BACKGROUND: The IFNL4-ΔG/TT (rs368234815) polymorphism controls production of the IFN-λ4 protein; the IFNL4-ΔG allele generates IFN-λ4, IFNL4-TT disrupts IFN-λ4 production. Individuals who carry IFNL4-ΔG have impaired clearance of hepatitis C virus (HCV), but less hepatic inflammation in the face of chronic hepatitis C.</p>
OBJECTIVE: To conduct a focused phenotype association study to identify additional manifestations of IFNL4-ΔG/TT.</p>
DESIGN: In the UK Biobank Cohort, we analyzed inpatient data from 401,239 White participants with a directly assayed IFNL4-ΔG/TT genotype, of whom 176,555 also provided primary care (outpatient) data. We selected 266 phenotypes with potential biological relevance to IFN-λ4 and created logistic regression models to estimate odds ratios (ORs) for associations between IFNL4-ΔG/TT genotype and these phenotypes in inpatients and outpatients.</p>
RESULTS: Three phenotypes yielded consistent findings (P < 0.05) in both databases. For hepatitis A virus (HAV) infection, we found a novel protective association for IFNL4-ΔG carriers (outpatient: OR = 0.77, P = 0.0005; inpatient: OR = 0.62, P = 0.015). IFNL4-ΔG was also associated with increased risk for HCV infection (outpatient: OR = 1.51, P = 0.025; inpatient: OR = 1.24, P = 0.036) and protectively associated with giant cell arteritis (GCA; outpatient: OR = 0.79, P = 0.038; inpatient: OR = 0.88, P = 0.047). Based on calculations that combined inpatient and outpatient data and corrected for multiple comparisons, the association between IFNL4-ΔG and HAV was statistically significant (P = 0.00004), while those for HCV and GCA were not.</p>
CONCLUSION: We report a novel protective association between the IFNL4-ΔG allele, which generates IFN-λ4 protein, and HAV infection. Future studies might examine the mechanism for this association and the therapeutic potential of IFN-λ4 for treating infection with HAV.</p>
17 Keywords
- Adult
- Aged
- Biological Specimen Banks
- Cohort Studies
- Female
- Genetic Predisposition to Disease
- Genotype
- Hepatitis A
- Humans
- Interferon Lambda
- Interleukins
- Male
- Middle Aged
- Phenotype
- Polymorphism, Single Nucleotide
- UK Biobank
- United Kingdom
10 Authors
- Neha Agarwala
- Minkyo Song
- Marc G Ghany
- Aubrey K Hubbard
- William Wheeler
- Eric Engels
- Ludmila Prokunina-Olsson
- Mitchell J Machiela
- Ruth M Pfeiffer
- Thomas R O'Brien
Enabling scientific discoveries that improve human health