Li Chongyi, Xiong Yanli, Zhong Zhaoyang, Zhang Shiheng, Peng Yu, Wang Lin'ang, Dai Nan, Li Mengxia, Ren Tao, Gan Lixia, Wang Dong
Cancer Center, Daping Hospital and Research Institute of Surgery, The Third Military Medical University, Chongqing, 400042, China.
Department of Biochemistry and Molecular Biology, The Third Military Medical University, Chongqing, 400042, China.
Cell Biochem Biophys. 2015 May;72(1):221-5. doi: 10.1007/s12013-014-0441-3.
A disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is considered to be an important anti-angiogenic protein, in which the first TSR domain is crucial for its anti-angiogenic activity. Previous study showed that ADAMTS5 plays a role in suppression of hepatocellular carcinoma (HCC) progression through its anti-angiogenic activity. The rs2380585 G>A single-nucleotide polymorphism (SNP) is a missense mutation, located in the ADAMTS5 first TSR domain coding sequence (CDS). In this study, we investigated the impacts of ADAMTS5 rs2380585 polymorphism on the risk and progress of hepatocellular carcinoma. A total of 220 HCC patients and 220 controls in a Chinese Han population were enrolled and genotyped. The associations between SNPs and HCC incidence and progression were analyzed with logistic regression model. We found that individuals with the ADAMTS5 rs2380585 A allele was significantly associated with decreased HCC risk (OR = 0.348, 95 % CI 0.236-0.512; p = 0.000). Individuals having the ADAMTS5 rs2380585 polymorphic genotype (GA+AA) had an OR of 0.348 (95 % CI 0.201-0.600; p = 0.000) for developing HCC, compared with individuals having the ADAMTS5 rs2380585 ancestral genotype. However, stratified analyses did not find any evident gene-covariates interaction. The SNP of rs2380585 was irrelevant to the frequencies of clinicopathological characteristics. Our results for the first time indicate that ADAMTS5 rs2380585 polymorphism contributes to HCC susceptibility.
含血小板反应蛋白基序的解聚素和金属蛋白酶5（ADAMTS5）被认为是一种重要的抗血管生成蛋白，其中第一个TSR结构域对其抗血管生成活性至关重要。先前的研究表明，ADAMTS5通过其抗血管生成活性在抑制肝细胞癌（HCC）进展中发挥作用。rs2380585 G>A单核苷酸多态性（SNP）是一种错义突变，位于ADAMTS5第一个TSR结构域编码序列（CDS）中。在本研究中，我们调查了ADAMTS5 rs2380585多态性对肝细胞癌风险和进展的影响。纳入了220例中国汉族人群的HCC患者和220例对照并进行基因分型。采用逻辑回归模型分析SNP与HCC发病率及进展之间的关联。我们发现，携带ADAMTS5 rs2380585 A等位基因的个体与HCC风险降低显著相关（OR = 0.348，95%CI 0.236 - 0.512；p = 0.000）。与携带ADAMTS5 rs2380585野生型基因型的个体相比，携带ADAMTS5 rs2380585多态性基因型（GA + AA）的个体发生HCC的OR为0.348（95%CI 0.201 - 0.600；p = 0.000）。然而，分层分析未发现任何明显的基因 - 协变量相互作用。rs2380585的SNP与临床病理特征频率无关。我们的结果首次表明，ADAMTS5 rs2380585多态性与HCC易感性有关。
