NTCP S267F variant associates with decreased susceptibility to HBV and HDV infection and decelerated progression of related liver diseases. (March 2019)

• Record Type: Journal Article
• Authors: Binh, Mai Thanh; Hoan, Nghiem Xuan; Van Tong, Hoang; Sy, Bui Tien; Trung, Ngo Tat; Bock, C.-Thomas; Toan, Nguyen Linh; Song, Le Huu; Bang, Mai Hong; Meyer, Christian G.; Kremsner, Peter G.; Velavan, Thirumalaisamy P.
• Is Part Of: International journal of infectious diseases. Volume 80(2019)
• Page Start: 147
• Page End: 152
• Publication Date: 2019-03
• Subjects: NTCP sodium taurocholate co-transporting polypeptide -- S267F substitution of serine at position 267 of NTCP with phenylalanine -- SNP single nucleotide polymorphism -- HC healthy control -- HBV hepatitis B virus -- HDV hepatitis delta virus -- CHB chronic hepatitis B -- LC liver cirrhosis -- HCC hepatocellular carcinoma -- HBsAg Hepatitis B surface antigen -- HDAg Hepatitis D antigen -- BCLC Barcelona Clinic Liver Cancer staging -- AFP alpha-fetoprotein -- PLT platelets -- AST and ALT aspartate and alanine amino transferase; HBV -- HDV -- NTCP -- S267F -- Liver diseases; Communicable diseases -- Periodicals; Communicable Diseases -- Periodicals; Communicable diseases; Periodicals; Electronic journals; 616.9
• DOI: 10.1016/j.ijid.2019.01.038
• Languages: English
• ISSNs: 1201-9712

Abstract

Highlights: The NTCP S267F variant is associated with a lower risk of chronic HBV infection. First study on NTCP S267F variant on concomitant HDV infection in Vietnamese population. The NTCP S267F is correlated with a reduced risk on clinical progression of liver cirrhosis and liver cancer. 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.