IFNL2 and Hepatitis C Virus Infection

The available evidence for the association between IFNL2 (Interleukin‑28A) and hepatitis C virus infection (MONDO_0005231) is limited. One population‐based study reported that the IL‑28A.rs12980602 TT genotype was significantly more frequent in healthy controls than in HCV‑infected subjects (PMID:30402710), suggesting a potential protective effect. However, a separate study in Han Chinese failed to show an association between polymorphisms across the IFN‑λ gene cluster and susceptibility to infection, although a rare haplotype was linked to altered biochemical parameters (PMID:24269996). Moreover, a functional assessment study demonstrated that IFNL2 expression, along with other IFN‑λ family members, is modulated in a sex‑dependent manner following viral mimic stimulation, supporting a role in the antiviral response (PMID:39423653).

In summary, the genetic evidence specific to IFNL2 is modest and derived from association studies with conflicting outcomes. The functional data, although not exclusive to IFNL2, provide supportive context by illustrating sex‐dependent differences in interferon responses. Taken together, while additional evidence may exist within the IFN‑λ gene cluster, the overall findings for IFNL2 suggest a limited but clinically informative association with HCV infection.

References

• Immunologic research • 2019 • Interleukin 28A.rs12980602 and interleukin 28B.rs8103142 genotypes could be protective against HCV infection PMID:30402710
• Infection, genetics and evolution • 2014 • Genetic polymorphisms of the IFNλ genes are associated with biochemical features in Han Chinese with HCV infection PMID:24269996
• Cytokine • 2024 • Evidence for a sex‑dependent effect modification in the association between IFN‑λ DNA polymorphisms and expression of IFN‑λ and interferon‑stimulated genes in human PBMC PMID:39423653

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