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MICA rs2596542 多态性与慢性丙型肝炎患者肝细胞癌风险的关联。

Association between MICA rs2596542 Polymorphism with the Risk of Hepatocellular Carcinoma in Chronic Hepatitis C Patients.

机构信息

Human Molecular Genetics Laboratory, Universidade Luterana do Brasil (ULBRA), Canoas, RS, Brazil.

Serviço de Gastroenterologia, Departamento de Medicina Interna, Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.

出版信息

Pathol Oncol Res. 2020 Jul;26(3):1519-1525. doi: 10.1007/s12253-019-00738-6. Epub 2019 Aug 31.

Abstract

In this study we investigated the impact of rs2596542A/G single nucleotide polymorphism (SNP) in the major histocompatibility complex class I chain-related sequence A (MICA) gene on HCV-induced hepatocellular carcinoma (HCC) susceptibility in a Brazilian population. In total, 252 HCV-infected patients (98 with HCV-induced HCC and 154 non-malignant HCV-induced liver cirrhosis) were enrolled and 98 healthy control subjects (negative anti-HCV). The MICA rs2596542 SNP genotypes were determined by real-time PCR assay. No differences in MICA genotype frequencies between HCV-induced cirrhosis patients and controls were observed. However, genotype frequencies of rs2596542A/G SNP were statistically different between HCV-induced HCC patients and controls (p = 0.048), and also between HCC and HCV-induced cirrhosis patients (p = 0.039). The highest frequency of the rs2596542AA genotype was observed in HCC patients (31.6%) when compared with HCV-induced cirrhosis patients (18.8%) and healthy controls (19.4%). Also, rs2596542AA genotype carriers have an increased risk for HCC when compared to HCV-induced cirrhosis status [odds ratio (OR) = 1.99; 95% confidence interval (CI) = 1.06-3.74, p = 0.020)] and healthy individuals (OR = 1.92, 95% CI = 1.00-3.70, p = 0.049). Taken together our study suggest that MICA rs2596542 SNP impacts HCV-induced HCC susceptibility suggesting that genetic variants in MICA are of clinical relevance to hepatocarcinogenesis by impacting host immune response in chronic HCV infection.

摘要

在这项研究中,我们调查了主要组织相容性复合体 I 类链相关序列 A(MICA)基因中 rs2596542A/G 单核苷酸多态性(SNP)对巴西人群中 HCV 诱导的肝细胞癌(HCC)易感性的影响。总共纳入了 252 名 HCV 感染患者(98 名 HCV 诱导的 HCC 患者和 154 名非恶性 HCV 诱导的肝硬化患者)和 98 名健康对照者(抗 HCV 阴性)。通过实时 PCR 检测确定 MICA rs2596542 基因型。在 HCV 诱导的肝硬化患者和对照组之间,MICA 基因型频率没有差异。然而,在 HCV 诱导的 HCC 患者和对照组之间(p=0.048)以及 HCC 和 HCV 诱导的肝硬化患者之间(p=0.039),rs2596542A/G SNP 基因型频率存在统计学差异。与 HCV 诱导的肝硬化患者(18.8%)和健康对照者(19.4%)相比,HCC 患者的 rs2596542AA 基因型频率最高(31.6%)。此外,与 HCV 诱导的肝硬化状态相比,rs2596542AA 基因型携带者发生 HCC 的风险增加[比值比(OR)=1.99;95%置信区间(CI)=1.06-3.74,p=0.020],与健康个体相比也增加(OR=1.92,95%CI=1.00-3.70,p=0.049)。综上所述,我们的研究表明,MICA rs2596542 SNP 影响 HCV 诱导的 HCC 易感性,表明 MICA 中的遗传变异通过影响慢性 HCV 感染中的宿主免疫反应,对肝癌发生具有临床相关性。

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