Dataset Information

Association between single-nucleotide polymorphisms and early spontaneous hepatitis B virus e antigen seroconversion in children.

ABSTRACT:

Background

The disease progression following hepatitis B virus (HBV) infection is associated with single-nucleotide polymorphisms (SNPs). However, the role of SNPs in chronic HBV infection in children remains unclear. Here, we investigate the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg) seroconversion in children with chronic hepatitis B infection.

Methods

This was a retrospective cohort study. We genotyped seven SNPs in the following genes, interleukin (IL)-10 (rs1800871 and rs1800872), human leukocyte antigen (HLA)-DPA1 (rs3077), HLA-DPB1 (rs9277535), HLA-DQB2 (rs7453920), HLA-DQB1 (rs2856718), and IL28B (rs8099917), in patients with chronic HBV infection using PCR and sequencing. These variants were analyzed for an association with early HBeAg seroconversion in children.

Results

Of 225 Japanese patients with chronic hepatitis B virus infection (male/female: 105/120, median age at initial visit: 6 years; range 0-44 years), 52 achieved spontaneous HBeAg seroconversion at the age of 10 years or younger (G1: early seroconversion group), and 57 did not achieve spontaneous HBeAg seroconversion under the age of 20 years (G2: late or no seroconversion group). Of the seven SNPs, only the HLA-DPA1 SNP displayed a low p-value (P = 0.070), but not significant, to have early HBeAg seroconversion in the dominant model and in the allele model (P = 0.073) using the chi-square test. The association study found a low p-value, but not significant, to have early HBeAg seroconversion in the dominant model for HLA-DPA1 (genotype TC + TT vs. CC, P = 0.070, odds ratio: 2.016, 95% confidence interval: 0.940-4.323) using a logistic regression model.

Conclusion

Although the HLA-DPA1 SNP did not show a statistically significant association with early HBeAg seroconversion in this study, the HLA-DPA1 SNP might increase the likelihood of achieving early spontaneous HBeAg seroconversion in children.

SUBMITTER: Komatsu H

PROVIDER: S-EPMC4230755 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Publications

Association between single-nucleotide polymorphisms and early spontaneous hepatitis B virus e antigen seroconversion in children.

Komatsu Haruki H Murakami Jun J Inui Ayano A Tsunoda Tomoyuki T Sogo Tsuyoshi T Fujisawa Tomoo T

BMC research notes 20141106

<h4>Background</h4>The disease progression following hepatitis B virus (HBV) infection is associated with single-nucleotide polymorphisms (SNPs). However, the role of SNPs in chronic HBV infection in children remains unclear. Here, we investigate the association between SNPs and early spontaneous hepatitis B e antigen (HBeAg) seroconversion in children with chronic hepatitis B infection.<h4>Methods</h4>This was a retrospective cohort study. We genotyped seven SNPs in the following genes, interle ...[more]

PMID: 25376093

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Project description:Background and aimsVarious inflammatory and immune cytokines play key roles in the progression of hepatitis B virus (HBV)-related liver cirrhosis (LC). This study explored the relationship between single nucleotide polymorphisms (SNPs) in cytokines with the combined effect of polymorphisms and gender-polymorphisms interaction and LC risk.MethodsIn this study, a case-control design was used, samples were selected from 45 patients with hepatitis B-related cirrhosis and 45 age-gender-matched chronic HBV-infected patients without cirrhosis attending the tumor hospital of Wuwei Academy of Medical Sciences. Fifteen SNPs were examined using a real-time polymerase chain reaction allelic discrimination system. Logistic regression was utilized to assess cytokine-associated SNPs and the association between SNPs and LC progression in HBV-infected patients.ResultsThe multivariate-adjusted logistic model revealed that the GG/AG dominant model (OR, 16.38; 95% CI, 1.13-236.70) and G allele (OR, 5.93; 95% CI, 0.98-36.01) of rs1800896 were associated with an increased risk of cirrhosis in CHB patients. Instead, rs2227306 CT presented a reduced cirrhosis risk (OR, 0.22; 95% CI, 0.04-1.38). Rs2055979 AA/AC was negatively associated with the risk of cirrhosis, potentially reversed in males (p = 0.021). Rs1799964 CC/CT was positively related to the risk of cirrhosis but reduced the risk of cirrhosis in males (OR, 0.13; 95% CI, 0.022-0.808; p = 0.028). Both rs1799964 TT and rs1799724 CT/TT genotype showed a synergistic effect in reducing the risk of cirrhosis with rs1800896 AA (OR, 0.08; 95% CI, 0.01-1.43 and OR, 0.12; 95% CI, 0.01-2.21).ConclusionPolymorphisms rs1800896 and rs2227306 are potentially associated with the risk of cirrhosis. For the first time, the study highlights that the rs2055979 AA/AC and rs1799964 CC/CT polymorphism interact with gender and its potential reversal of cirrhosis risk in males. Furthermore, rs1800896 AA showed a synergistic effect with rs1799964 TT and rs1799724 CT/TT to prevent the progression of HBV infection to cirrhosis.

Project description:Background and aimsCurrent guidelines are controversial regarding the continuation of nucleos(t)ide analogues (NAs) therapy after delivery in Hepatitis B virus (HBV)-infected pregnant women. The postpartum period may be an opportune moment for achieving hepatitis B e antigen (HBeAg) seroconversion earlier with constant NAs therapy due to the restoration of immune function after delivery. We investigated prenatal and pregnant factors associated with HBeAg seroconversion after pregnancy and developed a nomogram to predict HBeAg seroconversion rates, aiding decision-making for optimal management in women.MethodsWe retrospectively included 489 HBeAg-positive mothers as the training cohort from January 2014 to December 2018 and prospectively enrolled 94 patients as the external validation cohort from January 2019 to December 2021 at the First Affiliated Hospital of Xi'an Jiaotong University. In the training cohort, independent predictors were identified using the least absolute shrinkage and selection operator (LASSO) regression algorithm. Subsequently, multivariate logistic regression was employed to establish the nomogram. Model performance was assessed using the area under the receiver operating characteristic curve (AUC), calibration plots, and decision curve analysis (DCA). Both discrimination and calibration were evaluated through bootstrapping with 1,000 resamples. The external validation cohort was subsequently used to validate the nomogram.ResultsFactors such as pregnancy hepatitis flare (OR: 5.122, 95% CI: 2.725-9.928, p < 0.001), NAs therapy after delivery (OR: 15.051, 95% CI: 6.954-37.895, p: <0.001), hepatitis B surface antigen (HBsAg) (OR: 0.549, 95% CI: 0.366-0.812, p: 0.003) and HBV DNA level at delivery (OR: 0.785, 95% CI: 0.619-0.986, p: 0.041) were included in the final risk model. The AUC in the training set was 0.873 (95% CI: 0.839-0.904). The calibration curve of the nomogram closely resembled the ideal diagonal line. DCA showed a significantly better net benefit in the model. External validation also confirmed the reliability of the prediction nomogram. The AUC in the external validation set was 0.889 (95% CI: 0.801-0.953). The calibration curve for the external validation set was in close proximity to the ideal diagonal line. DCA also demonstrated a significant net benefit associated with the predictive model, consistent with the findings in the training set. Finally, the nomogram has been translated into an online risk calculator that is freely available to the public (https://wendyzhong.shinyapps.io/DynNomapp/).ConclusionWe developed a nomogram based on prenatal and pregnant factors to estimate HBeAg seroconversion after delivery in women. This tool provides clinicians with a precise and effective way to identify individuals likely to undergo HBeAg seroconversion postpartum, aiding in decision-making for optimal management.

Dataset Information

Association between single-nucleotide polymorphisms and early spontaneous hepatitis B virus e antigen seroconversion in children.

Background

Methods

Results

Conclusion

Publications

Association between single-nucleotide polymorphisms and early spontaneous hepatitis B virus e antigen seroconversion in children.

Similar Datasets

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