rs4803221

This is a protein-altering variant in the IFNL4 gene.

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GWAS Catalog Trait Associations (2)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

cirrhosis of liver

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)

Allele C

OR 0.14

p 3.0e-20

N 447,231

Major Consortium StudyLarge GWAS

European

liver disease

Verma A et al. “Diversity and scale: Genetic architecture of 2068 traits in the VA Million Veteran Program.” Science (new York, N.y.) 385(6706):eadj1182 (2024)

Allele C

OR 0.07

p 3.0e-14

N 611,644

Major Consortium StudyLarge GWAS

multi-ancestry

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Research that mentions this SNP (1)

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Association of IL28B variants with response to pegylated‐interferon alpha plus ribavirin combination therapy reveals intersubgenotypic differences between genotypes 2a and 2b

Meta-analysisN=23,717Naoya Sakamoto et al.(2011)· Journal of Medical Virology

Meta-analysis of 67 studies involving 20,163 patients for sustained virologic response (SVR) and 10 studies with 3,554 patients for spontaneous clearance (SC). IL28B polymorphisms showed strong associations with HCV clearance: rs12979860 (CC favorable) demonstrated similar associations across HCV genotypes and ethnicities (OR ~3.2-3.6), while rs8099917 (TT favorable) showed stronger effects in East Asians (OR ~6.3 vs 3.4 in Caucasians) and rs12980275 (AA favorable) had OR of 3.95 overall. All three SNPs showed genotype-dependent effects with HCV-1/4 having 3-fold higher ORs than HCV-2/3.

Traits studied:HCV treatment response to pegylated interferon-alpha and ribavirinHepatitis C virus (HCV) sustained virologic responseHepatitis C virus spontaneous clearance

PubMed DOI Metascience Observatory

About IFNL4

This gene is a polymorphic pseudogene which, in some humans, encodes the interferon (IFN) lambda 4 protein. Humans are polymorphic for the dinucleotide TT/deltaG allele. Compared to the ancestral state in non-human primates, the TT allele produces a frameshift in the coding region of this gene which is predicted to induce nonsense-mediated mRNA decay. This allele, and an allele in the first intron of this gene, have experienced a rapid increase in frequency and show indications of positive selection. The ancestral states of these alleles are associated with an impaired ability to clear hepatitis C virus. This gene, like other type III interferons (IFNs), interacts with the IFN lambda receptor complex (IFNLR) whose signaling is generally restricted to epithelial cells. This gene resides in a cluster of four type III IFN genes and at least two pseudogenes on chromosome 19q13.2. In general, interferons are produced in response to viral infection and block viral replication and propagation to uninfected cells by activating the JAK-STAT pathway and up-regulating antiviral genes. Multiple alternatively spliced transcripts have been described for this gene but their biological validity and protein coding status is still being ascertained. [provided by RefSeq, May 2017]