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Int J Infect Dis. 2019 Mar;80:147-152. doi: 10.1016/j.ijid.2019.01.038. Epub 2019 Jan 24.

NTCP S267F variant associates with decreased susceptibility to HBV and HDV infection and decelerated progression of related liver diseases.

Author information

1
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Vietnamese-German Center for Medical Research, Hanoi, Vietnam; 108 Military Central Hospital, Hanoi, Vietnam.
2
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Vietnamese-German Center for Medical Research, Hanoi, Vietnam; Vietnam Military Medical University, Hanoi, Vietnam.
3
Vietnamese-German Center for Medical Research, Hanoi, Vietnam; 108 Military Central Hospital, Hanoi, Vietnam.
4
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Department of Infectious Diseases, Robert Koch Institute, Berlin, Germany.
5
Vietnamese-German Center for Medical Research, Hanoi, Vietnam; Vietnam Military Medical University, Hanoi, Vietnam.
6
108 Military Central Hospital, Hanoi, Vietnam.
7
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Vietnamese-German Center for Medical Research, Hanoi, Vietnam; Duy Tan University, Da Nang, Vietnam.
8
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany.
9
Institute of Tropical Medicine, University of Tübingen, Tübingen, Germany; Vietnamese-German Center for Medical Research, Hanoi, Vietnam; Duy Tan University, Da Nang, Vietnam. Electronic address: velavan@medizin.uni-tuebingen.de.

Abstract

OBJECTIVES:

To determine potential associations of the rs2296651 variant (c.800C>T, S267F) of NTCP with HBV and HBV plus concomitant HDV infection as well as with the progression of related liver diseases.

METHODS:

The S267F variant was genotyped by DNA sequencing in 620 HBV-infected patients and 214 healthy controls (HCs). Among the patients, 450 individuals were tested for HDV by a nested PCR assay. Logistic regression was applied to examine the association.

RESULTS:

The S267F variant was found more frequently among HCs (16%) compared to HBV-infected (6%) and HBV-HDV co-infected patients (3%) (HBV patients vs HC: OR=0.32, P=0.00002 and HDV patients vs. HC: OR=0.17, P=0.018). The frequency of S267F variant was inversely correlated with CHB, LC or HCC patients compared with HCs (OR=0.31, P=0.001; OR=0.32, P=0.013; OR=0.34, P=0.002, respectively). S267F variant was also associated with decreased risk of the development of advanced liver cirrhosis (LC) and hepatocellular carcinoma (HCC) (Child B and C vs. Child A, OR=0.26, adjusted P=0.016; BCLC B,C,D vs. BCLC A, OR=0.038, P=0.045, respectively). In addition, patients with the genotype CT had lower levels of AST, ALT, total and direct bilirubin as well as higher platelet counts, indicating an association with a more favorable clinical outcome.

CONCLUSION:

The NTCP S267F variant of the SLC10A1 gene exhibits protective effects against HBV and HDV infection and is associated with a reduced risk of developing to advanced stages of LC and HCC.

KEYWORDS:

HBV; HDV; Liver diseases; NTCP; S267F

PMID:
30685591
DOI:
10.1016/j.ijid.2019.01.038
[Indexed for MEDLINE]
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