Human leukocyte antigen variants and risk of hepatocellular carcinoma modified by hepatitis C virus genotypes: A genome-wide association study.
Hepatology
; 67(2): 651-661, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-28921602
ABSTRACT
We conducted a genome-wide association study to discover genetic variants associated with hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC). We genotyped 502 HCC cases and 749 non-HCC controls using the Axiom-CHB genome-wide array. After identifying single-nucleotide polymorphism clusters located in the human leukocyte antigen (HLA) region which were potentially associated with HCC, HLA-DQB1 genotyping was performed to analyze 994 anti-HCV seropositives collected in the period 1991-2013 in a community-based cohort for evaluating long-term predictability of HLA variants for identifying the risk of HCC. Cox proportional hazards models were used to estimate the hazard ratios and 95% confidence intervals of HLA genotypes for determining the aforementioned HCC risk. Eight single-nucleotide polymorphisms in the proximity of HLA-DQB1 were associated with HCC (P < 8.7 × 10-8 ) in the genome-wide association study. Long-term follow-up showed a significant association with HLA-DQB1*0301 and DQB1*0602 (P < 0.05). The adjusted hazard ratios associated with HCC were 0.45 (0.30-0.68) and 2.11 (1.34-3.34) for DQB1*0301 and DQB1*0602, respectively. After stratification by HCV genotypes, DQB1*0301 showed protective effects only in patients with HCV genotype 1, whereas DQB1*0602 conferred risk of HCC only in patients with HCV non-1 genotypes. HLA imputation analyses revealed that HLA-DRB1*1501, which is in linkage disequilibrium with DQB1*0602, also increased the risk of HCC (odds ratio, 1.96; 95% confidence interval, 1.31-2.93). Haplotype analysis supported that DQB1*0301 and DQB1*0602 are primarily protective and susceptible variants, respectively. Conclusion:
HLA-DQB1 was independently associated with HCC; HCV genotypes modified the effects of HLA-DQB1 on the risk of HCC. (Hepatology 2018;67651-661).
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Hepacivirus
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Carcinoma Hepatocelular
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Polimorfismo de Nucleotídeo Único
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Estudo de Associação Genômica Ampla
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Cadeias beta de HLA-DQ
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Neoplasias Hepáticas
Tipo de estudo:
Etiology_studies
/
Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article