Novel Polymorphism in the Promoter Region of HLA-DQB1 Is a Predictor of Anti-HCV Therapy Response

  Hepatitis C virus (HCV) is a major cause of chronic liver infection, which may lead to liver cirrhosis, fibrosis, and hepatocellular carcinoma while about one-fourth of the infected patients recover spontaneously. The host immune response remains decisive in the outcomes of antiviral treatment. Single nucleotide polymorphisms (SNPs) at the genes within the human leukocyte antigen (HLA) cluster are associated with differential immune response and treatment outcomes. This study aimed to determine the association of SNPs in Tumor necrosis factor-alpha (TNF-) and HLA genes (HLA-DRB1and HLA-DQB1) with the outcomes of HCV infection and anti-HCV therapy. The study included 245 HCV-infected patients visiting a tertiary care hospital, located in Islamabad, Pakistan. Viral quantificationandgenotyping were performed by real-timePCR. Twenty SNPs in TNF-, HLA-DRB1, andHLA-DQB1 were sequence-genotyped by the Sanger method in 180 patients. Multivariate logistic regression was performed to establish the association of SNPs with spontaneous clearance of the virus and response to anti-HCV therapy. Five out of 20 SNPs were novel. Allelic variants at three different locations (HLA-DRB1, rs2308802; HLA-DQB1,-8447, and HLADQB1,- 8471) showed significant associations with two groups of HCV patients receiving anti-HCV treatment (responsive and nonresponsive). Multivariate analyses disclosed that genotype A/A at HLA-DQB1 (-8471) was a significant predictor of positive response to treatment although in the presence of the variant at HLA-DRB1 (rs230880) (P = 0.004). However, no association was detected between the haplotypes constructed for the three sets of SNPs and different categories of patients. This study established a novel SNP HLA-DQB1(-8471) as an important predictor of an effective response to anti-HCV therapy in HCV-infected Pakistani patients. Prescreening of this variant before therapy would benefit HCV patients.