Lee MH, et al. - A genome-wide association study (GWAS) was performed to identify genetic variants associated with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). Researchers reported an independent association between HLA-DQB1 with HCC. In addition, HCV genotypes modified the impacts of HLA-DQB1 on the risk of HCC.

Methods

• Using the Axiom-CHB genome-wide array, 502 HCC cases and 749 non-HCC controls were genotyped.
• HLA-DQB1genotyping was performed to analyze 994 anti-HCV seropositives collected in the period of 1991-2013 in a community-based cohort for assessing long-term predictability of HLA variants for identifying HCC risk, after identifying single nucleotide polymorphism (SNP) cluster located in the human leukocyte antigen region which were potentially associated with HCC.
• Using Cox proportional hazards models, researchers estimated the hazard ratios (HRs) and 95% confidence intervals (CIs) of HLA genotypes for determining the aforementioned HCC risk.

Results

• Findings demonstrated that eight SNPs in the proximity of HLA-DQB1 were associated with HCC (p < 8.7 × 10^-8) in GWAS.
• A significant association with HLA-DQB1*03:01 and DQB1*06:02 (p < 0.05) was demonstrated in long-term follow-up.
• Data reported that the adjusted HRs associated with HCC were 0.45 (0.30-0.68) and 2.11 (1.34-3.34) forDQB1*03:01 and DQB1*06:02, respectively.
• Post- stratification by HCV genotypes, protective effects of DQB1*03:01 were seen only in patients with HCV genotype 1, whereas DQB1*06:02 conferred risk of HCC only in patients with HCV non-1 genotypes.
• HLA-DRB1*15:01, which is in linkage disequilibrium with DQB1*06:02, also increased the risk of HCC (odds ratio = 1.96, 95% CI = 1.31-2.93), as highlighted in HLA imputation analyses.
• In addition, haplotype analysis supported that DQB1*03:01 and DQB1*06:02 are primary protective and susceptible variants, respectively.