Su Zhenzhen, Li Yi, Liao Yun, Cai Bei, Chen Jie, Zhang Junlong, Li Lixin, Ying Binwu, Tao Chuanmin, Wang Lanlan
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, PR China.
Infect Genet Evol. 2014 Oct;27:77-82. doi: 10.1016/j.meegid.2014.07.001. Epub 2014 Jul 8.
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.
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.
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.
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.
近年来，牛磺胆酸钠共转运多肽（NTCP）被新鉴定为乙型肝炎病毒（HBV）受体，这在一定程度上揭示了HBV嗜肝性及其宿主特异性的原因。然而，相关研究仅限于体外或动物实验。因此，本研究旨在探讨NTCP基因多态性与人类HBV自然病程的关系。
根据血清学和临床特征，将933名中国汉族个体分为两大组，352名病毒清除对照组和581名持续感染患者。后者包括186例肝细胞癌（HCC）患者和395例非HCC患者。从HapMap数据集中选择了总共5个单核苷酸多态性（SNP），并通过高分辨率熔解（HRM）曲线法进行基因分型。
rs7154439 AA基因型在病毒清除组中的观察频率略高于持续感染组[16例（4.5%）受试者 vs. 10例（1.7%）受试者。共显性模型中p = 0.008，调整优势比（AOR）= 0.33，95%置信区间（CI）= 0.15 - 0.75；隐性模型中p = 0.006，AOR = 0.32，95% CI = 0.14 - 0.72]。而rs4646287 AA基因型在HCC组中的观察频率略高于非HCC组[6例（3.2%）受试者 vs. 1例（0.3%）受试者。共显性模型中p = 0.018，AOR = 15.74，95% CI = 1.59 - 155.54；隐性模型中p = 0.018，AOR = 15.91，95% CI = 1.61 - 157.01]。两组之间的等位基因或单倍型分布无统计学显著差异。
本研究表明，NTCP区域的多态性可能与HBV感染的自然病程有关。rs7154439 AA基因型与HBV清除有关，而rs4646287 AA基因型与HCC发生有关。然而，考虑到样本量相对较小，需要进行更大规模的研究，尤其是通过多中心合作，以充分验证这些发现的意义。
