Zhenzhen Su1, Yi Li1, Yun Liao1, Bei Cai1, Jie Chen1, Junlong Zhang1, Lixin Li1, Binwu Ying1, Chuanmin Tao1, Lanlan Wang2. 1. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. 2. Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China. Electronic address: wanglanlan_med@163.com.
Abstract
OBJECTIVE: In recent years, sodium taurocholate cotransporting polypeptide (NTCP) was newly identified as a hepatitis B virus (HBV) receptor, which partly shed light on the reason for HBV hepatotropism and its host specificity. However, the related researches were limited to in vitro or animal experiments. Therefore, this study aimed to investigate the association of NTCP polymorphisms with HBV natural course in humans. METHODS: According to their serological and clinical characteristics, 933 Chinese Han individuals were divided into two major groups, 352 viral clearance controls and 581 persistently infected patients. The latter one included 186 hepatocellular carcinoma (HCC) and 395 non-HCC subjects. A total of five single nucleotide polymorphisms (SNPs) were selected from HapMap dataset and genotyped by high resolution melting (HRM) curve method. RESULTS: The rs7154439 AA genotype was observed slightly more common in viral clearance group than in persistently infected group [16 (4.5%) subjects vs. 10 (1.7%) subjects. p=0.008, adjusted odds ratio (AOR)=0.33, 95% confidence interval (CI)=0.15-0.75 in a codominant model; and p=0.006, AOR=0.32, 95% CI=0.14-0.72 in a recessive model]. While the rs4646287 AA genotype was observed slightly more frequent in HCC group than in non-HCC group [6 (3.2%) subjects vs. 1 (0.3%) subject. p=0.018, AOR=15.74, 95% CI=1.59-155.54 in a codominant model; and p=0.018, AOR=15.91, 95% CI=1.61-157.01 in a recessive model]. There were no statistically significant differences of allele or haplotype distribution between any two groups. CONCLUSIONS: This study suggests that polymorphisms in the NTCP region may be associated with the natural course of HBV infection. The rs7154439 AA genotype was associated with HBV clearance, while the rs4646287 AA genotype was associated with HCC occurrence. However, considering the sample size is relatively small, larger studies, especially through multicenter collaboration will be needed to fully validate the significance of these findings.
OBJECTIVE: In recent years, sodium taurocholate cotransporting polypeptide (NTCP) was newly identified as a hepatitis B virus (HBV) receptor, which partly shed light on the reason for HBV hepatotropism and its host specificity. However, the related researches were limited to in vitro or animal experiments. Therefore, this study aimed to investigate the association of NTCP polymorphisms with HBV natural course in humans. METHODS: According to their serological and clinical characteristics, 933 Chinese Han individuals were divided into two major groups, 352 viral clearance controls and 581 persistently infectedpatients. The latter one included 186 hepatocellular carcinoma (HCC) and 395 non-HCC subjects. A total of five single nucleotide polymorphisms (SNPs) were selected from HapMap dataset and genotyped by high resolution melting (HRM) curve method. RESULTS: The rs7154439 AA genotype was observed slightly more common in viral clearance group than in persistently infected group [16 (4.5%) subjects vs. 10 (1.7%) subjects. p=0.008, adjusted odds ratio (AOR)=0.33, 95% confidence interval (CI)=0.15-0.75 in a codominant model; and p=0.006, AOR=0.32, 95% CI=0.14-0.72 in a recessive model]. While the rs4646287 AA genotype was observed slightly more frequent in HCC group than in non-HCC group [6 (3.2%) subjects vs. 1 (0.3%) subject. p=0.018, AOR=15.74, 95% CI=1.59-155.54 in a codominant model; and p=0.018, AOR=15.91, 95% CI=1.61-157.01 in a recessive model]. There were no statistically significant differences of allele or haplotype distribution between any two groups. CONCLUSIONS: This study suggests that polymorphisms in the NTCP region may be associated with the natural course of HBV infection. The rs7154439 AA genotype was associated with HBV clearance, while the rs4646287 AA genotype was associated with HCC occurrence. However, considering the sample size is relatively small, larger studies, especially through multicenter collaboration will be needed to fully validate the significance of these findings.
Authors: Eric Nyarko; Christian Obirikorang; W K B A Owiredu; Evans Asamoah Adu; Emmanuel Acheampong; Freeman Aidoo; Emmanuel Ofori; Bright Selorm Addy; Henry Asare-Anane Journal: Virol J Date: 2020-07-03 Impact factor: 4.099