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

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 < 10-4 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 × 10-12; rs1110446: OR = 1.79, P = 1.66 × 10-13; and rs3094137: OR = 1.73, P = 7.09 × 10-9). 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 × 10-4) 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-A*33:03 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.

journal_name

Sci Rep

journal_title

Scientific reports

authors

Sawai H,Nishida N,Khor SS,Honda M,Sugiyama M,Baba N,Yamada K,Sawada N,Tsugane S,Koike K,Kondo Y,Yatsuhashi H,Nagaoka S,Taketomi A,Fukai M,Kurosaki M,Izumi N,Kang JH,Murata K,Hino K,Nishina S,Matsumoto A,Tanaka

doi

10.1038/s41598-018-26217-7

subject

Has Abstract

pub_date

2018-05-21 00:00:00

pages

7958

issue

1

issn

2045-2322

pii

10.1038/s41598-018-26217-7

journal_volume

8

pub_type

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