Association between NTCP gene polymorphisms with disease progression of hepatitis B infection.

Authors

  • N. Tuyapala Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • S. Payungporn Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.
  • P. Tangkijvanich Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand.

Keywords:

Hepatitis B virus (HBV), chronic HBV infection (CHB), spontaneous HBV clearance, hepatocellular carcinoma (HCC), single nucleotide polymorphisms (SNPs), sodium dependent taurocholate co-transporting polypeptide (NTCP)

Abstract

Background : Sodium taurocholate co-transporting polypeptide (NTCP) has been recently identified as the cellular receptor of hepatitis B virus (HBV). In addition, nucleotide polymorphisms (SNPs) in the NTCP gene are shown to be associated with developing chronic HBV infection in the Han Chinese population. However, it is unclear whether SNPs are related to the clinical outcome of HBV infection in the Thai population.

Objective : The aim of this study was to investigate the association of NTCP polymorphism with chronic HBV infection (CHB) and HCC progression.

Methods : We recruited 242 healthy controls without previous HBV exposure, 230 individuals with spontaneous HBV clearance and 635 patients with chronic hepatitis B (CHB). Among the CHB group, 319 patients were diagnosed with hepatocellular carcinoma (HCC). SNPs (rs2296651) of NTCP were detected by allelic discrimination assay using real-time polymerase chain reaction with TaqMan probe. Statistical analysis was performed using unpaired t-test, analysis of variance (ANOVA) and Chi-square test.

Results : The frequencies of GG, GA and AA genotypes of rs2296651 in healthy controls were 74.2%, 22.1% and 3.7%, respectively. The corresponding genotypes in the HBV clearance group were 84.1% 15.1% and 0.8%, while their frequencies in the CHB group were 85.0%, 13.4% and 1.6%, respectively. Compared with healthy controls, the distribution of non-GG (GA and AA) genotypes were significantly lower in the HBV clearance group [odds ratio (OR) 0.54; 95 % CI (0.35 - 0.86), P = 0.001] and the CHB groups (0.51; 0.35 - 0.73, P < 0.001). However, there was no difference in their frequencies between the HBV clearance and CHB groups. The role of SNPs in relation to HCC development was further analyzed in the CHB groups. There was no difference in the distribution of SNP between patients with or without HCC.

Conclusion : In this report, GA or AA genotypes of rs2296651 were more prevalence in non-HBV infected population. However, SNP rs2296651 did not contribute to spontaneous HBV clearance, developing CHB and HCC occurrence.

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References

Bosch FX, Ribes J, Diaz M, Cleries R. Primary liver cancer: worldwide incidence and trends. Gastroenterology 2004;127(5 Suppl 1):S5-16. https://doi.org/10.1053/j.gastro.2004.09.011

El Serag HB. Hepatocellular carcinoma. N Engl J Med 2011;365:1118-27.

https://doi.org/10.1056/NEJMra1001683

European Association for the Study of the Liver. EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012;57:167-85. https://doi.org/10.1016/j.jhep.2012.02.010

Yan H, Zhong G, Xu G, He W, Jing Z, Gao Z, et al. Sodium taurocholatecotransporting polypeptide is a functional receptor for human hepatitis B and D virus. Elife 2012;1:e00049.

https://doi.org/10.7554/eLife.00049

Jung D, Fried M, Kullak-Ublick GA. Human apical sodium-dependent bile salt transporter gene (SLC10A2) is regulated by the peroxisome proliferator-activated receptor alpha. J Biol Chem 2002;277:30559-66. https://doi.org/10.1074/jbc.M203511200

Kullak-Ublick GA, Stieger B, Meier PJ. Enterohepatic bile salt transporters in normal physiology and liver disease. Gastroenterology 2004;126:322-42. https://doi.org/10.1053/j.gastro.2003.06.005

Li W. The hepatitis B virus receptor. Annu Rev Cell Dev Biol 2015;31:125-47.

https://doi.org/10.1146/annurev-cellbio-100814-125241

Su Z, Li Y, Liao Y, Cai B, Chen J, Zhang J, et al. Association of the gene polymorphisms in sodium taurocholatecotransporting polypeptide with the outcomes of hepatitis B infection in Chinese Han population. Infect Genet Evol 2014;27:77-82. https://doi.org/10.1016/j.meegid.2014.07.001

Peng L, Zhao Q, Li Q, Li M, Li C, Xu T, et al. The p.Ser267Phe variant in SLC10A1 is associated with resistance to chronic hepatitis B. Hepatology 2015;61:1251-60. https://doi.org/10.1002/hep.27608

Yang J, Yang Y, Xia M, Wang L, Zhou W, Yang Y, et al. A genetic variant of the NTCP gene is associated with HBV infection status in a Chinese population. BMC cancer 2016;16: 211.

https://doi.org/10.1186/s12885-016-2257-6

Hu HH, Liu J, Lin YL, Luo WS, Chu YJ, Chang CL, et al. The rs2296651 (S267F) variant on NTCP (SLC10A1) is inversely associated with chronic hepatitis B and progression to cirrhosis and hepatocellular carcinoma in patients with chronic hepatitis B. Gut 2016; 65:1514-21.

https://doi.org/10.1136/gutjnl-2015-310686

Su Z, Li Y, Liao Y, Cai B, Chen J, Zhang J, et al. Polymorphisms in sodium taurocholatecotransporting polypeptide are not associated with hepatitis B virus clearance in Chinese Tibetans and Uygurs. Infect Genet Evol 2016;41:128-34. https://doi.org/10.1016/j.meegid.2016.03.039

Ho RH, Leake BF, Roberts RL, Lee W, Kim RB. Ethnicity-dependent polymorphism in Na+- taurocholatecotransporting polypeptide (SLC10A1) reveals a domain critical for bile acid substrate recognition. J BiolChem 2004; 279:7213-22. https://doi.org/10.1074/jbc.M305782200

Li N, Zhang P, Yang C, Zhu Q, Li Z, Li F, et al. Association of genetic variation of sodium taurocholatecotransporting polypeptide with chronic hepatitis B virus infection. Genet Test Mol Biomarkers 2014;18:425-9. https://doi.org/10.1089/gtmb.2013.0491

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Published

2023-08-21

How to Cite

1.
Tuyapala N, Payungporn S, Tangkijvanich P. Association between NTCP gene polymorphisms with disease progression of hepatitis B infection. Chula Med J [Internet]. 2023 Aug. 21 [cited 2024 Oct. 12];62(6). Available from: https://he05.tci-thaijo.org/index.php/CMJ/article/view/399