Role of HLA DRB1 Alleles and Allele Zygosity in Susceptibility to or Protection from HCV Infection in Hemodialysis Patients

Abstract

Hepatitis C virus (HCV) infection affects more than 170 million people worldwide and Egypt has the highest prevalence in the world resulting in high morbidity and mortality from chronic liver disease, cirrhosis and hepatocellular carcinoma. T cell responses against HCV are regulated by the host's human leukocyte antigen (HLA) alleles, thus are ideal candidate genes to investigate for associations with HCV infection. We aimed to identify associations of HLA DRB1 alleles with HCV infection in a high risk of exposure to HCV population, chronic kidney disease (CKD) patients on dialysis and to study any possible relationships with allele zygosity. The study population comprised of 110 HCV infected and 143 HCV uninfected CKD patients undergoing regular hemodialysis. We found a significant negative association between HLA-DRB1*03 and HCV infection but the association did not retain significance after adjustment for multiple comparisons. HLA DRB1*03 was found at reduced frequency in HCV antibody-positive compared to HCV antibody-negative CKD patients on regular dialysis (corrected P was not significant). No significant associations between HCV infection and HLA DRB1 zygosity were observed. Our results suggest that there is minimal evidence for a significant role of a particular HLA DRB1 allele or allele zygosity in the susceptibility or protection to HCV in high risk hemodialysis patients with similar exposure to infection. Extended haplotype and additional studies are warranted to identify potential genetic alleles imparting resistance to HCV infection.