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Genome-wide association study identified new susceptible genetic variants in HLA class I region for hepatitis B virus-related hepatocellular carcinoma. | LitMetric

AI Article Synopsis

  • - The study involved a genome-wide association study (GWAS) focused on identifying genetic factors associated with HBV-related liver cancer (HCC) among Japanese individuals, including 473 HCC patients and 516 HBV carriers.
  • - Researchers found 65 significant SNPs in the HLA class I region, and confirmed three of these SNPs through further analysis, showing strong links to HCC risk in multiple East Asian populations.
  • - The study also highlighted a specific HLA allele (HLA-A 33:03) linked to disease progression to HCC, but additional genetic influences in the HLA class I region were suggested since conditioning on HLA did not eliminate the associations of the three SNPs.

Article Abstract

We have performed a genome-wide association study (GWAS) including 473 Japanese HBV (hepatitis B virus)-positive HCC (hepatocellular carcinoma) patients and 516 HBV carriers including chronic hepatitis and asymptomatic carrier individuals to identify new host genetic factors associated with HBV-derived HCC in Japanese and other East Asian populations. We identified 65 SNPs with P values < 10 located within the HLA class I region and three SNPs were genotyped in three independent population-based replication sets. Meta-analysis confirmed the association of the three SNPs (rs2523961: OR = 1.73, P = 7.50 × 10; rs1110446: OR = 1.79, P = 1.66 × 10; and rs3094137: OR = 1.73, P = 7.09 × 10). We then performed two-field HLA genotype imputation for six HLA loci using genotyping data to investigate the association between HLA alleles and HCC. HLA allele association testing revealed that HLA-A 33:03 (OR = 1.97, P = 4.58 × 10) was significantly associated with disease progression to HCC. Conditioning analysis of each of the three SNPs on the HLA class I region abolished the association of HLA-A33:03 with disease progression to HCC. However, conditioning the HLA allele could not eliminate the association of the three SNPs, suggesting that additional genetic factors may exist in the HLA class I region.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5962604PMC
http://dx.doi.org/10.1038/s41598-018-26217-7DOI Listing

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