Published online Oct 7, 2021. doi: 10.3748/wjg.v27.i37.6262
Peer-review started: April 8, 2021
First decision: June 26, 2021
Revised: July 6, 2021
Accepted: September 1, 2021
Article in press: September 1, 2021
Published online: October 7, 2021
Genome-wide association studies (GWASs) in Asian populations indicate that the HLA-DP and HLA-DQ loci are involved in the persistence of hepatitis B virus (HBV) infections. Persistent viral replication and inflammation are key influencers in HBV-related carcinogenesis.
HBV-related single nucleotide polymorphisms (SNPs) have been identified in east Asian populations but are uncommon in African populations. Different mechanisms may drive persistent infection in those regions.
We examined genetic and nongenetic factors associated with persistent HBV infection and viral load in families with hepatocellular carcinoma (HCC).
HCC families were enrolled. Five HBV-related SNPs (rs477515, rs9272105, rs9276370, rs7756516, and rs9277535) were genotyped. Factors associated with persistent HBV infection and viral load were identified with the use of generalized estimating equations.
In the first-stage persistent HBV study, all SNPs except rs9272105 were associated with persistent infection. A significantly higher contribution of nongenetic than genetic factors (P < 0.001) to persistent HBV infection was found. In the second-stage viral load study, sex, relationship with index case, rs477515, rs9272105, and rs7756516 were associated with viral load. Receiver operating characteristic curve, and genetic and nongenetic factors had equal effects on viral load in the HCC family cohort (P = 0.3117).
GWAS identified SNPs that have roles in persistent HBV infection and HBV viral loads in an HCC family cohort. Nongenetic factors were more important than genetic factors in persistent HBV infection but had equal contributions to HBV viral load. HBV-related SNPs resulting in high viral loads in parents may drive persistent infection in East Asian populations. The mechanism of persistent HBV infection-related SNPs involves a prolonged viral replication phase in East Asian adults.
Termination of the HBV replication phase before pregnancy will be a therapeutic goal in East Asian countries.