title: Patient HLA-DRB1* and -DQB1* allele and haplotype association with hepatitis C virus persistence and clearance.
abstract: Hepatitis C virus (HCV) infection is prevalent throughout the world and interferon (IFN)-based treatments are currently the only therapeutic option. However, depending upon variations in their human leukocyte antigen (HLA), some patients do not respond well to IFN therapy. The current study evaluated the HLA allele and haplotype distribution of 204 HCV-seropositive individuals from Islamabad, Pakistan, who were receiving standard IFN therapy. In this cohort, 150 patients (74%) showed a sustained virological response to IFN therapy, whereas 54 (26%) did not. In addition to the HCV patients, 102 unrelated healthy volunteers were used as controls. DNA was isolated from the blood of the patients and controls for HLA-DRB1 and HLA-DQB1 allele typing, whilst plasma was used for HCV detection and genotyping. HLA-DRB1*04 was found to impart a significant protective advantage [Bonferroni-corrected P value (pc)=0.047] against HCV infection. In patients on IFN therapy, HLA-DRB1*11 and -DQB1*0301 (pc=0.044) were found to be associated with viral clearance. In contrast, HLA-DRB1*07 (pc=0.008) individually or in combination with HLA-DQB1*02 was found to be associated with viral persistence. These associations of HLA with HCV persistence or clearance will be beneficial in deciding the therapeutic regimen for Pakistani patients infected with HCV genotype 3a.
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
authors.forename: Lubna
authors.initials: L
authors.lastname: Ali
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
authors.forename: Atika
authors.initials: A
authors.lastname: Mansoor
authors.affiliation: Institute of Developmental Genetics, HelmHoltz Zentrum München, Neuherberg, Germany.|Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
authors.forename: Nafees
authors.initials: N
authors.lastname: Ahmad
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
authors.forename: Saima
authors.initials: S
authors.lastname: Siddiqi
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
authors.forename: Kehkashan
authors.initials: K
authors.lastname: Mazhar
authors.affiliation: Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
authors.forename: Ambreen G
authors.initials: AG
authors.lastname: Muazzam
authors.affiliation: Shifa College of Medicine, Pitras Bokhari Road H-8/4, Islamabad 44000, Pakistan.|COMSATS Institute of Information Technology, Park Road, Chak Shahzad, Islamabad 44000, Pakistan.
authors.forename: Raheel
authors.initials: R
authors.lastname: Qamar
authors.affiliation: Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46000, Pakistan.
authors.forename: Khalid M
authors.initials: KM
authors.lastname: Khan
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000998:Antiviral Agents / Q000276:immunology / Q000627:therapeutic use; D005260:Female; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D016174:Hepacivirus / Q000276:immunology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D007372:Interferons / Q000276:immunology* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010154:Pakistan; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D007372:Interferons