UGT2B28 genomic variation is associated with hepatitis B e-antigen seroconversion in response to antiviral therapy.
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 × 10-8and 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 < 200 IU/ml and ALT/AST ratio <2 (n = 132; P = 0.013, HR = 10.538, CI = 1.420-78.196).
Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.
Kung-Hao
KH
Liang
Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.|Chang Gung University, College of Medicine, Taiwan.
Chih-Lang
CL
Lin
Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Chang Gung University, College of Medicine, Taiwan.
Chao-Wei
CW
Hsu
Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Chang Gung University, College of Medicine, Taiwan.
Ming-Wei
MW
Lai
Liver Research Unit, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan.
Rong-Nan
RN
Chien
Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan.|Molecular Medicine Research Center, Chang Gung University, Taoyuan, Taiwan.|Chang Gung University, College of Medicine, Taiwan.
Chau-Ting
CT
Yeh
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