Genetic variations of NTCP are associated with susceptibility to HBV infection and related hepatocellular carcinoma

et al. 2020

Preprint

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.

Section: Resultssupporting

confidence: 88%

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

et al. 2020

Preprint

Section: Discussionsupporting

confidence: 87%

“…With the high risk of HBV infection and its associated end-stage liver complications, the lack of a cure for HBV infection, high treatment cost [10,11], low long term benefits and high toxicity associated with interferon, nucleoside and nucleotide therapies; new treatments and methods targeting different molecules are warranted. Single nucleotide polymorphic (SNP) variants of the NTCP gene -SLC10A1 such as rs7154439, rs4646287 [4,12,13], rs2296651 and rs61745930 [14][15][16] is associated with HBV persistent infection (chronicity), expression of HBeAg and viral clearance among different ethnic groups and countries. The polymorphic SNP variants in the Ghanaian population or responsible for any of the HBV infection status are non-existent.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

Virol J

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.

“…These ndings are similar to those reported among Korean (3.1%) and Chinese-Americans (7.5%) populations [14]. Also, similar ndings have been replicated among Chinese and Vietnamese in a study by Wang, et al [13]. Moreover, Li, et al [15]reported a 4.4% MAF of rs2296651 among the Chinese Han population.…”

Section: Discussionsupporting

confidence: 85%

“…With the high risk of HBV infection and its associated end-stage liver complications, the lack of a cure for HBV infection, high treatment cost [10,11], low long term bene ts and high toxicity associated with interferon, nucleoside and nucleotide therapies; new treatments and methods targeting different molecules are warranted. Single nucleotide polymorphic (SNP) variants of the NTCP gene -SLC10A1 such as rs7154439, rs4646287 [4,12,13], rs2296651 and rs61745930 [14][15][16] is associated with HBV persistent infection (chronicity), expression of HBeAg and viral clearance among different ethnic groups and countries. The polymorphic SNP variants in the Ghanaian population or responsible for any of the HBV infection status are non-existent.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

Preprint

Abstract 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.