UGT2B28 genomic variation is associated with hepatitis B e-antigen seroconversion in response to antiviral therapy.

ABSTRACT: Seroconversion of hepatitis B virus (HBV) e-antigen (HBeAg) is a critical but often-missed therapeutic goal in standard antiviral treatments. An extreme-phenotype genome-wide association study was performed, comparing untreated spontaneous recoverers (with seroconversion of HBV surface antigen) versus entecavir-treated patients failing to achieve HBeAg seroconversion. A single-nucleotide-polymorphism rs2132039 on the UGT2B28 gene, alongside an adjacent copy number polymorphism (CNP605), manifested the strongest clinical associations (P?=?3.4?×?10(-8) and 0.001, respectively). Multivariate analysis showed that rs2132039-TT genotypes, but not CNP605 copy numbers, remained associated to spontaneous recoverers (P?=?0.009). The clinical association of rs2132039 was validated successfully in an independent cohort (n?=?302; P?=?0.002). Longitudinal case-only analyses revealed that the rs2132039-TT genotype predicted shorter time-to-HBeAg-seroconversion in all antiviral-treated patients (n?=?380, P?=?0.012), as well as the peginterferon-treated subgroup (n?=?123; P?=?0.024, Hazard ratio [HR]?=?2.104, Confidence interval [CI]?=?1.105-4.007). In the entecavir-treated subgroup, the predictive effect was restricted by pretreatment alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, with effective prediction observed in patients with ALT?

SUBMITTER: Liang KH 

PROVIDER: S-EPMC5036189 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature