title: Lack of a strong association between HLA class II, tumour necrosis factor and transporter associated with antigen processing gene polymorphisms and virological response to alpha-interferon treatment in patients with chronic hepatitis C.
abstract: The aim of the study was to investigate whether polymorphisms of the HLA class II, tumour necrosis factor (TNF) and transporter associated with antigen processing (TAP) genes influence the response to alpha-interferon in patients with chronic hepatitis C. Twenty-seven sustained responders and 55 non-responders to alpha-interferon monotherapy were investigated. HLA-DRB1, DQA1, DQB1, TNFA, TNFB, TAP1 and TAP2 alleles were determined by PCR-based molecular techniques. Sustained virological response was defined as undetectable serum hepatitis C virus (HCV) RNA for at least 3 years after the end of treatment. Probability (P) values were corrected for the number of alleles tested (Pc). Viral genotype 1b was more frequent in responders than in non-responders (56% vs. 26%, P = 0.009). HLA-DQB1*02 occurred less frequently in responders than in non-responders (14.8% vs. 29%, Pc not significant). HLA-DRB1*11 and DQB1*0602 were found in 22.2% and 9.3% of responders and in 10.9% and 1.8% of non-responders, respectively (Pc not significant). There was no difference in the distribution of TNF alleles in the two groups. Twenty-four (88.8%) responder patients as compared with 34 (61.8%) non-responders were TAP1*0101 homozygous (Pc not significant). Thus, in European Caucasoids with chronic hepatitis C, we could not demonstrate a strong association between HLA class II, TNF, and TAP gene polymorphisms and response to interferon treatment.
authors.affiliation: Department of Gastroenterology and Hepatology 'Crespi', Niguarda Hospital, Milan, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Airoldi
authors.forename: C
authors.initials: C
authors.lastname: Zavaglia
authors.forename: E
authors.initials: E
authors.lastname: Silini
authors.forename: C
authors.initials: C
authors.lastname: Tinelli
authors.forename: M
authors.initials: M
authors.lastname: Martinetti
authors.forename: M
authors.initials: M
authors.lastname: Asti
authors.forename: A
authors.initials: A
authors.lastname: Rossini
authors.forename: M
authors.initials: M
authors.lastname: Vangeli
authors.forename: L
authors.initials: L
authors.lastname: Salvaneschi
authors.forename: G
authors.initials: G
authors.lastname: Pinzello
mesh_terms: D018528:ATP-Binding Cassette Transporters; D000998:Antiviral Agents / Q000494:pharmacology*; D002908:Chronic Disease; D005260:Female; D016174:Hepacivirus / Q000187:drug effects; D006526:Hepatitis C / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000276:immunology*; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D018528:ATP-Binding Cassette Transporters; D000998:Antiviral Agents; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D016898:Interferon-alpha; D014409:Tumor Necrosis Factor-alpha; C477327:transporter associated with antigen processing (TAP)