Mai Thanh Binh1, Nghiem Xuan Hoan1, Hoang Van Tong2, Bui Tien Sy3, Ngo Tat Trung3, C-Thomas Bock4, Nguyen Linh Toan5, Le Huu Song3, Mai Hong Bang6, Christian G Meyer7, Peter G Kremsner8, Thirumalaisamy P Velavan9. 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.
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-infectedpatients 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-infectedpatients (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.
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