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- Title
Polymorphism of estrogen receptor alpha (ESR1) is associated with virological response to entecavir (ETV) in nucleoside-naïve adult patients with chronic hepatitis B.
- Authors
Zhang, T.-t.; Ye, J.; Xia, S.-l.; Zhang, Y.-f.; Su, Q.; Zhang, Z.-h.; Li, X.
- Abstract
Introduction: Polymorphisms in estrogen receptor alpha (ESR1) are reported to be associated with the susceptibility to persistent HBV infection, HBV liver cirrhosis and HBV-related hepatocellular carcinoma (HCC). Materials and methods: To test the hypothesis that polymorphisms in estrogen receptor alpha (ESR1) might influence the virological response to entecavir (ETV) therapy, we examined two polymorphisms (PvuII and XbaI) in 76 nucleoside-naïve chronic hepatitis B (CHB) patients. All of the patients (52 HBeAg-positive and 24 HBeAg-negative) were treated with ETV 0.5 mg daily and followed up for a median time of 96 weeks (range 48-96). Polymorphisms were determined using the polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) method. Results: Under an additive model, the univariate analysis showed that patients carrying the PvuII T/C genotype might have higher virological responders than those carrying the T/T and C/C genotypes at week 48 (87.7 vs. 57.1 vs. 58.3 %; P = 0.012) and week 96 (96.7 vs. 64.3 vs. 24 87.5 %; P = 0.018), although this difference disappeared with the multiple analysis at week 48 [95 % confidence interval (CI) 0.687-3.841; P = 0.269] and week 96 (95 % CI 0.861-18.016; P = 0.077). Conversely, the univariate analysis suggests statistical significance between the recessive model of PvuII (TT vs. TC/CC) and virological response at week 48 (57.1 vs. 81.1 %; P = 0.033) and week 96 (64.3 vs. 94.7 %; P = 0.017). Multiple regression analysis affirmed the significant and independent association between the recessive model of PvuII and virological response. In other words, patients carrying at least one PvuII C allele (TC/CC) had a better likelihood of achieving virological response compared with those carrying the T/T genotype at week 48 (95 % CI 1.026-14.785, P = 0.046) and week 96 (95 % CI 1.456-57.509; P = 0.018). XbaI polymorphisms were not significantly associated with virological response. Conclusion: Our results suggest that the PvuII polymorphism may play an important role in determining ETV efficacy after 48 and 96 weeks of treatment, at least in this study population.
- Subjects
CHINA; ACADEMIC medical centers; ANTIVIRAL agents; CHI-squared test; CONFIDENCE intervals; FISHER exact test; GENETIC polymorphisms; HEALTH outcome assessment; POLYMERASE chain reaction; RESEARCH funding; T-test (Statistics); U-statistics; MULTIPLE regression analysis; TREATMENT effectiveness; DATA analysis software; DESCRIPTIVE statistics; CHRONIC hepatitis B; GENETICS
- Publication
Infection, 2013, Vol 41, Issue 2, p371
- ISSN
0300-8126
- Publication type
Article
- DOI
10.1007/s15010-012-0320-z