Large-scale genome-wide association study identifies HLA class II variants associated with chronic HBV infection: a study from Taiwan Biobank.
Aliment Pharmacol Ther
; 52(4): 682-691, 2020 08.
Article
in En
| MEDLINE
| ID: mdl-32573827
ABSTRACT
BACKGROUND:
Chronic hepatitis B virus (HBV) infection is a great health burden with geographical variations.AIMS:
To explore genetic variants associated with chronic HBV infection.METHODS:
The study included 15 352 participants seropositive for HBV core antibodies in Taiwan Biobank. Among them, 2591 (16.9%) seropositive for HBV surface antigen (HBsAg) were defined as having chronic HBV infection. All participants were examined for whole-genome genotyping by Axiom-Taiwan Biobank Array. The human leucocyte antigen (HLA) imputation was performed after identification of the variants within the region. Logistic regressions were used to estimate odds ratios (ORs) with 95% confidence intervals. Correlations of different HLA allele frequencies with HBsAg seroprevalence were evaluated across worldwide populations by Pearson correlation coefficients. Epitope prediction was performed for HLA alleles using NetMHCIIpan method.RESULTS:
Located within a cluster of 450 single nucleotide polymorphisms in HLA class II, rs7770370 (P = 2.73 × 10-35 ) was significantly associated with HBV chronicity (Pcorrected < 8.6 × 10-8 ). Imputation analyses showed that HLA-DPA1*0202 and HLA-DPB1*0501 were associated with chronic HBV, with adjusted ORs of 1.43 (1.09-1.89) and 1.61 (1.29-2.01). These allele frequencies were positively correlated with global HBsAg seroprevalence, with R of 0.75 and 0.62 respectively (P < 0.05). HLA-DRB1*1302, HLA-DQA1* 0102 and HLA-DQB1*0609 associated with HBV chronicity negatively, with adjusted ORs of 0.31 (0.17-0.58), 0.70 (0.56-0.87) and 0.33 (0.18-0.63). These HLA alleles had various binding affinities to the predicted epitopes derived from HBV nucleocapsid protein.CONCLUSIONS:
HLA class II variants are relevant for chronicity after HBV acquisition.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Genes, MHC Class II
/
Hepatitis B, Chronic
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Polymorphism, Single Nucleotide
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Genome-Wide Association Study
Type of study:
Risk_factors_studies
Limits:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Asia
Language:
En
Journal:
Aliment Pharmacol Ther
Journal subject:
FARMACOLOGIA
/
GASTROENTEROLOGIA
/
TERAPIA POR MEDICAMENTOS
Year:
2020
Type:
Article
Affiliation country:
Taiwan