genetic contribution of endoplasmic reticulum aminopeptidase 1 polymorphisms to liver fibrosis progression in patients with hcv infection

The endoplasmic reticulum aminopeptidase erap1 regulates innate and adaptive immune responses, trimming peptides and loading onto hla class i molecules. coding single nucleotide polymorphisms within erap1 are associated with autoimmune diseases, viral infections, and cancer development. our purpose was to analyze the influence of erap1 variants on fibrogenesis in hepatitis c virus (hcv)–infected patients. a range of erap1 polymorphisms were genotyped in 722 unrelated caucasian patients diagnosed with chronic hcv from two spanish cohorts. patients were classified according to their fibrosis stage. paraffin-embedded tissue microarrays were constructed to assess erap1 expression (hcv = 38; alcoholic = 20) by immunohistochemistry. a statistical algorithm was applied to derive a fibrogenesis prediction model. the erap1 variants rs30187/t (k528, pc < 0.001) and rs27044/g (q730, pc < 0.001) were related with severe fibrosis. these results were validated in the two independent cohorts. furthermore, patients with the rs30187/t allele had stronger erap1 protein expression than those with the rs30187/c (p < 0.05). the statistical model showed that patients with rs30187 c/t and t/t genotypes took 15.58 years (median) to develop advanced fibrosis, but this value was 32.08 years in patients carrying c/c genotype (p < 0.005). erap1 variants influence the clinical course of fibrogenesis in hcv-infected patients. these polymorphisms could be exploited as constitutive new markers of fibrosis evolution. the results highlight the possibility of using modulators of erap1 to generate a protective immune response against chronic hcv infection. what is known what is new here potential translational impact