Patient HLA-DRB1* and -DQB1* allele and haplotype association with hepatitis C virus persistence and clearance.
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.
Ali
Lubna
L
Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
Mansoor
Atika
A
Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
Ahmad
Nafees
N
Institute of Developmental Genetics, HelmHoltz Zentrum München, Neuherberg, Germany.|Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
Siddiqi
Saima
S
Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
Mazhar
Kehkashan
K
Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
Muazzam
Ambreen G
AG
Institute of Biomedical and Genetic Engineering (IBGE), PO Box No. 2891, Islamabad 44000, Pakistan.
Qamar
Raheel
R
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.
Khan
Khalid M
KM
Pir Mehr Ali Shah Arid Agriculture University, Rawalpindi 46000, Pakistan.
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
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