DNMT3A -448A>G polymorphism and the risk for hepatocellular carcinoma.
DNMT3A -448A>G polymorphism and the risk for hepatocellular carcinoma.
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DOI：
10.3892/br.2013.121
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发表时间：
2013-07
影响因子：
2.3
通讯作者：
Chengcheng Zhao;Feng Yan;Huazhang Wu;Fengchang Qiao;X. Qiu;H. Fan
中科院分区：
文献类型：
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作者：
Chengcheng Zhao;Feng Yan;Huazhang Wu;Fengchang Qiao;X. Qiu;H. Fan
DNA 甲基转移酶 (DNMT) 3A 在致癌过程中发挥着重要作用。先前的一项研究结果表明，DNMT3A -448A>G 单核苷酸多态性 (SNP) 与胃癌 (GC) 和结直肠癌 (CRC) 的易感性之间存在关联。肝细胞癌（HCC）是一种常见的恶性肿瘤，其表达模式与GC相似。本病例对照研究的目的是确定 DNMT3A 基因多态性与 HCC 易感性之间是否存在关联。采用实时定量PCR（qPCR）检测13例HCC患者的肿瘤和非癌肝组织中DNMT3A的表达。通过聚合酶链式反应/限制性片段长度多态性（PCR-RFLP）检测到DNMT3A表达增加，以及DNMT3A启动子的-448A>G多态性，并通过测序证实。在 108 名 HCC 患者和 225 名年龄和性别匹配的健康对照中检查了 -448A>G 多态性的分布。根据患者年龄和性别进行分层分析，评估DNMT3A-448A>G多态性与HCC风险的相关性。 HCC患者和对照组的-448A等位基因频率分别为24.07%和24.22%。 GG、AG、AA基因型频率分别为55.56 vs. 56.89%、40.74 vs. 37.78%、3.7 vs. 5.33%。结果表明，-448A>G 与 HCC 易感性无关，尽管 -448A>G 是功能性单核苷酸多态性 (SNP)，并增加了 HCC 病例中 DNMT3A 的表达。本研究的结果表明，DNMT3A -448A>G 多态性不足以预测 HCC 易感性的生物标志物。
DNA-methyltransferase (DNMT) 3A plays a significant role in carcinogenesis. Findings of a previous study suggested an association between the DNMT3A -448A>G single-nucleotide polymorphism (SNP) and susceptibility to gastric cancer (GC) and colorectal cancer (CRC). Hepatocellular carcinoma (HCC) is a common malignancy, with a similar expression pattern to GC. The aim of this case-control study was to determine whether there is an association between DNMT3A gene polymorphism and susceptibility to HCC. Real-time quantitive PCR (qPCR) was employed to detect DNMT3A expression in tumor and non-cancer liver tissue from 13 HCC patients. An increased expression of DNMT3A was detected, as well as -448A>G polymorphisms of DNMT3A promoter by polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP), confirmed by sequencing. The distribution of -448A>G polymorphisms was examined in 108 HCC patients and 225 healthy controls who were matched for age and gender. The association of -448A>G polymorphisms of DNMT3A and the risk of HCC was evaluated by stratified analysis according to the patient's age and gender. The allele frequency of -448A among HCC patients and the controls was 24.07 vs. 24.22%, respectively. The frequency of genotypes GG, AG, AA was 55.56 vs. 56.89%, 40.74 vs. 37.78%, 3.7 vs. 5.33%, respectively. The results indicated that -448A>G is not associated with susceptibility to HCC, although -448A>G is a functional single-nucleotide polymorphism (SNP) and increased the expression of DNMT3A in HCC cases. Findings of the present study suggested that the DNMT3A -448A>G polymorphism is an insufficient biomarker to predict the susceptibility to HCC.