Association Between a Variant in ADAMTS5 and the Susceptibility to Hepatocellular Carcinoma in a Chinese Han Population.

Abstract

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.