Hepatitis B virus infection in Taiwan: The role of NTCP rs2296651 variant in relation to sex

Nfor, Oswald Ndi; Wu, Ming-Fang; Debnath, Tonmoy; Lee, C.-T.; Lee, W.; Liu, W.-H.; Tantoh, Disline Manli; Hsu, Shu‐Yi; Liaw, Yung‐Po

doi:10.1111/jvh.12912

Cited by 13 publications

(11 citation statements)

References 23 publications

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“…The NTCP p.Ser267Phe mutation cannot completely block HBV infection in vivo for 8.57% (15/175) of p.Ser267Phe mutation homozygotes were reported to be HBV-infected. In detail, 6 of 32 homozygotes in our cohort, 5 of 42 homozygotes in Hu's study (Hu et al, 2016), 2 of 2 homozygotes in Wang's study (Wang et al, 2017), 1 of 2 homozygotes in An's study (An et al, 2018), 1 of 12 homozygotes in Zhang's study (Zhang et al, 2017), and 0 of 85 homozygotes in Nfor's study (Nfor et al, 2018) were reported to be HBV infection. The HBV-infected p.Ser267Phe mutation homozygotes all had low or negative viral loads.…”

Section: Discussionmentioning

confidence: 58%

Diverse Effects of the NTCP p.Ser267Phe Variant on Disease Progression During Chronic HBV Infection and on HBV preS1 Variability

Yang

et al. 2019

Front. Cell. Infect. Microbiol.

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The sodium taurocholate co-transporting polypeptide (NTCP) acts as a cellular receptor for the hepatitis B virus (HBV) infection on host hepatocytes. We aim to investigate how the NTCP p.Ser267Phe variant affects HBV-related disease progression and analyze viral genomic variability under a host genetic background carrying the p.Ser267Phe variant. A total of 3187 chronic hepatitis B (CHB) patients were enrolled and genotyped for the p.Ser267Phe variant. The variant's association with disease progression was evaluated by logistic regression analysis. We also enrolled 83 treatment-naive CHB patients to analyze the variability of the HBV preS1 region. The frequency of the NTCP p.Ser267Phe variant was significantly lower in patients diagnosed with acute-on-chronic liver failure [OR (95% CI) = 0.33 (0.18–0.58), P = 1.34 × 10 −4 ], cirrhosis [OR (95% CI) = 0.47 (0.31–0.72), P = 4.04 × 10 −4 ], and hepatocellular carcinoma [OR (95% CI) = 0.54 (0.34–0.86), P = 9.83 × 10 −3 ] as compared with CHB controls under the additive model after adjustment. Furthermore, the percentage of amino acid mutations in HBV preS1 region was significantly higher in the NTCP p.Ser267Phe heterozygote group than in the NTCP wild type homozygote group ( P < 0.05). We herein demonstrate that the NTCP p.Ser267Phe variant is a protective factor reducing CHB patient risk for liver failure, cirrhosis, and hepatocellular carcinoma. A host genetic background carrying NTCP p.Ser267Phe exerts selective pressure on the virus, leading to more variability.

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Section: Discussionmentioning

confidence: 58%

Diverse Effects of the NTCP p.Ser267Phe Variant on Disease Progression During Chronic HBV Infection and on HBV preS1 Variability

Yang

et al. 2019

Front. Cell. Infect. Microbiol.

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“…Several studies have indicated that variants of rs2296651 either increases an individual's susceptibility to HBV infection and/or its complications, makes resolution/viral clearance of the infection faster or improves the prognostic outcome of cirrhosis and HCC [15,[19][20][21][22]. The evidence of the transferability of rs2296651 associated with HBV infection has been demonstrated among the Han population [15], Taiwanese [24] and Vietnamese [19]. The study has some limitations that should be acknowledged.…”

Section: Resultsmentioning

confidence: 95%

NTCP gene polymorphisms and Hepatitis B virus infection status in a Ghanaian population

Nyarko

Obirikorang

Owiredu

et al. 2020

Preprint

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Abstract BackgroundSLC10A1 gene codes NTCP, a receptor through which the hepatitis B virus (HBV) gets access into hepatocytes - a stage of the viral cycle necessary for replication. Polymorphism variants of SLC10A1 play roles in HBV infection, viral clearance, treatment outcome, and complications, in diverse ethnic groups and countries. However, no such study has been conducted in the Ghanaian population, a country with HBV endemicity. Therefore, an exploratory study was conducted to investigate the presence of three (3) single nucleotide polymorphisms (SNPs) in the SLC10A1 gene (rs2296651, rs61745930, and rs4646287) and assessed the risk of HBV infection among the Ghanaian population.MethodPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the presence of the SNPs among 292 participants comprising 146 HBV infected persons as case-subjects and 146 HBV non-infected persons as control-subjects. ResultsThe minor allele frequency (T) of rs2296651 was present in a significantly high proportion of cases compared with the control group (12.6% vs. 3.1%, p < 0.0001). The homozygote recessive variant of rs61745930 was present in 2.7% of the control group and 5.5% of the case group. Moreover, the minor allele frequencies of rs4646287 were 9.6% and 8.6% among the control and the case group, respectively (p = 0.767). Under the dominant (CC) genetic model of inheritance, rs2296651 was found to be protective of HBV infection [OR = 0.18 (0.07–0.44)], whereas under the co-dominant and additive model, rs2296651 was a potential risk factor for HBV infection [OR = 5.2 (95%CI: 2.1–12.8); 3.5 (95%CI: 1.6–7.6], respectively. Variants of rs61745930 and rs4646287 were not associated with HBV infection (p > 0.05). Polymorphisms in SLC10A1, however, did not show any significant association with HBV infectivity (p > 0.05).ConclusionThe study highlights some polymorphism proof that variants rs2296651, rs61745930, and rs4646287 exist in HBV-infected individuals in Ghana. Variant rs2296651 was found to be associated with HBV infection. Nonetheless, polymorphisms in SLC10A1 were not associated with HBV infectivity among the Ghanaian population. Further investigation is warranted to assess the offensive role of the relationship between rs2296651 and HBV infectivity.

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“…Several studies have reported the presence of SLC10A1 rs2296651, rs61745930, and rs4646287 SNP variants among persons with HBV infection (4,14,24). Thus, we determined the association between 3 SNPs in the SLC10A1 gene (rs2296651, rs61745930, and rs4646287) and the risk of HBV infection among the Ghanaian population.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have indicated that variants of rs2296651 either increases an individual's susceptibility to HBV infection and/or its complications, makes resolution/viral clearance of the infection faster or improves the prognostic outcome of cirrhosis and HCC [15,[19][20][21][22]. The evidence of the transferability of rs2296651 associated with HBV infection has been demonstrated among the Han population [15], Taiwanese [24] and Vietnamese [19]. However, unlike our results, rs2296651 [(c.800C > T) (S267F)] has been associated with reduced HBV infection and associated hepatic complications [25].…”

Section: Discussionmentioning

confidence: 99%

NTCP gene polymorphisms and hepatitis B virus infection status in a Ghanaian population

Nyarko

Obirikorang

Owiredu

et al. 2020

Virol J

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Background: SLC10A1 gene codes NTCP, a receptor through which the hepatitis B virus (HBV) gets access into hepatocytes-a stage of the viral cycle necessary for replication. Polymorphism variants of SLC10A1 play roles in HBV infection, viral clearance, treatment outcome, and complications, in diverse ethnic groups and countries. However, no such study has been conducted in the Ghanaian population, a country with HBV endemicity. Therefore, an exploratory study was conducted to investigate the presence of three (3) single nucleotide polymorphisms (SNPs) in the SLC10A1 gene (rs2296651, rs61745930, and rs4646287) and assessed the risk of HBV infection among the Ghanaian population. Method: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to determine the presence of the SNPs among 292 participants comprising 146 HBV infected persons as case-subjects and 146 HBV non-infected persons as control-subjects. Results: The minor allele frequency (T) of rs2296651 was present in a significantly high proportion of cases compared with the control group (11.6% vs. 3.1%, p < 0.0001). The homozygote recessive variant of rs61745930 was present in 2.7% of the control group and 5.5% of the case group. Moreover, the minor allele frequencies of rs4646287 were 9.3 and 8.2% among the control and the case group, respectively (p = 0.767). Under the dominant (CC) genetic model of inheritance, rs2296651 was found to be protective of HBV infection [OR = 0.18 (0.07-0.44)], whereas under the co-dominant and additive model, rs2296651 was a potential risk factor for HBV infection [OR = 5.2 (95%CI: 2.1-12.8); 3.5 (95%CI: 1.6-7.6], respectively. Variants of rs61745930 and rs4646287 were not associated with HBV infection (p > 0.05). Polymorphisms in SLC10A1, however, did not show any significant association with HBV infectivity (p > 0.05). Conclusion: The study highlights some polymorphism proof that variants rs2296651, rs61745930, and rs4646287 exist in HBV-infected individuals in Ghana. Although variant rs2296651 was found to be associated with HBV infection, this association warrants more studies. Polymorphisms in SLC10A1 were not associated with HBV infectivity among the Ghanaian population. Further investigation is warranted to assess the offensive role of the relationship between rs2296651 and HBV infectivity.

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Hepatitis B virus infection in Taiwan: The role of NTCP rs2296651 variant in relation to sex

Cited by 13 publications

References 23 publications

Diverse Effects of the NTCP p.Ser267Phe Variant on Disease Progression During Chronic HBV Infection and on HBV preS1 Variability

Diverse Effects of the NTCP p.Ser267Phe Variant on Disease Progression During Chronic HBV Infection and on HBV preS1 Variability

NTCP gene polymorphisms and Hepatitis B virus infection status in a Ghanaian population

NTCP gene polymorphisms and hepatitis B virus infection status in a Ghanaian population

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