Genetic contribution of endoplasmic reticulum aminopeptidase 1 polymorphisms to liver fibrosis progression in patients w
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ORIGINAL ARTICLE
Genetic contribution of endoplasmic reticulum aminopeptidase 1 polymorphisms to liver fibrosis progression in patients with HCV infection Jose Ramón Vidal-Castiñeira 1 & Antonio López-Vázquez 1,2 & Paula Diaz-Bulnes 1 & Susana Díaz-Coto 3 & Leonardo Márquez-Kisinousky 1 & Jesús Martínez-Borra 1,2 & Carmen A. Navascues 4 & Paloma Sanz-Cameno 5 & Juan de la Vega 6 & Aurora Astudillo 7 & Manuel Rodríguez 4 & Carlos López-Larrea 1,2 Received: 10 March 2020 / Revised: 24 June 2020 / Accepted: 30 June 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract 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 may 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. Key messages What is known & &
Several ERAP1 polymorphisms are associated with autoimmune diseases and cancer. ERAP1 trims peptides to HLA class I presentation.
What is new here & &
ERAP1 polymorphisms are associated with fibrogenesis. The ERAP1 polymorphisms genotype could help us in clinical management of patients.
* Carlos López-Larrea [email protected] 1
Translational Immunology Laboratory, Health Research Institute of the Principality of Asturias (ISPA), Hospital Universitario Central de Asturias, Oviedo, Spain
2
Immunology Service, Hospital Universitario Central de Asturias, Av. de Roma s/n, 33011 Oviedo, Spain
3
Statistical Department, Universidad de Oviedo, Oviedo, Spain
4
Gastroenterology Service, Hospital Universitario Central de Asturias, Oviedo, Spain
5
Liver Unit, Gastroenterology Service,
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