TGFBR3 多态性及其单倍型与慢性乙型肝炎病毒感染和肝细胞癌发生的年龄相关。

TGFBR3 polymorphisms and its haplotypes associated with chronic hepatitis B virus infection and age of hepatocellular carcinoma occurrence.

机构信息

Department of Life Science, Sogang University, Seoul, Korea.

出版信息

Dig Dis. 2011;29(3):278-83. doi: 10.1159/000327559. Epub 2011 Aug 9.

DOI:10.1159/000327559

PMID:21829018

Abstract

OBJECTIVE

Hepatocellular carcinoma (HCC) is one of the most common cancers and is mainly caused by viral infections including hepatitis B virus (HBV). Recently, the decreased expression level of the transforming growth factor, beta receptor III (TGFBR3) gene, has been implicated in HCC and other human cancers. This study investigated whether TGFBR3 polymorphisms might be associated with HBV clearance and HCC occurrence.

METHODS

This study identified 27 single nucleotide polymorphisms (SNPs) in the exon, promoter, and exon-intron boundary regions of TGFBR3 by resequencing in 24 individuals. Then, 9 SNPs in the promoter and exons of the gene were genotyped from 1,065 Koreans composed of 637 chronic carriers (CC) and 428 spontaneously recovered (SR) subjects.

RESULTS

Two SNPs, rs1805113 (Phe676Phe) in exon 13 and rs1805117 in 3'-UTR (p = 0.009 and p = 0.008, respectively) were significantly associated with HBV clearance. In addition, Cox relative hazards analyses revealed that haplotype BL2_ht2 showed a significant association with the age of HCC occurrence among chronic HBV patients (relative hazard = 1.38; p = 0.007).

CONCLUSION

Our findings suggest that TGFBR3 polymorphisms and its haplotypes might be associated with HBV clearance and age of HCC occurrence.

摘要

目的

肝细胞癌（HCC）是最常见的癌症之一，主要由病毒感染引起，包括乙型肝炎病毒（HBV）。最近，转化生长因子β受体 III（TGFBR3）基因的表达水平降低与 HCC 和其他人类癌症有关。本研究探讨 TGFBR3 多态性是否与 HBV 清除和 HCC 发生有关。

方法

本研究通过对 24 个人进行重测序，鉴定了 TGFBR3 外显子、启动子和外显子-内含子边界区域的 27 个单核苷酸多态性（SNP）。然后，从由 637 名慢性携带者（CC）和 428 名自发性恢复（SR）个体组成的 1065 名韩国人中，对基因启动子和外显子中的 9 个 SNP 进行了基因分型。

结果

两个 SNP，外显子 13 中的 rs1805113（Phe676Phe）和 3'-UTR 中的 rs1805117（p = 0.009 和 p = 0.008）与 HBV 清除显著相关。此外，Cox 相对危险度分析显示，慢性 HBV 患者中 BL2_ht2 单倍型与 HCC 发生年龄显著相关（相对危险度=1.38；p = 0.007）。