1. NTCP S267F variant associates with decreased susceptibility to HBV and HDV infection and decelerated progression of related liver diseases.
- Author
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Binh MT, Hoan NX, Van Tong H, Sy BT, Trung NT, Bock CT, Toan NL, Song LH, Bang MH, Meyer CG, Kremsner PG, and Velavan TP
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Alanine Transaminase metabolism, Alleles, Aspartate Aminotransferases metabolism, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular genetics, Case-Control Studies, Coinfection, Disease Progression, Female, Genetic Predisposition to Disease, Genotype, Hepatitis B genetics, Hepatitis D genetics, Humans, Liver Cirrhosis diagnosis, Liver Cirrhosis genetics, Liver Diseases genetics, Liver Neoplasms diagnosis, Liver Neoplasms genetics, Male, Middle Aged, RNA, Viral isolation & purification, Risk Factors, Sequence Analysis, DNA, Vietnam epidemiology, Young Adult, Genetic Variation, Hepatitis B epidemiology, Hepatitis D epidemiology, Liver Diseases diagnosis, Organic Anion Transporters, Sodium-Dependent genetics, Symporters genetics
- 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., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2019
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