De Benedittis Carla, Bellan Mattia, Crevola Martina, Boin Elena, Barbaglia Matteo Nazzareno, Mallela Venkata Ramana, Ravanini Paolo, Ceriani Elisa, Fangazio Stefano, Sainaghi Pier Paolo, Burlone Michela Emma, Minisini Rosalba, Pirisi Mario
Department of Translational Medicine, Università del Piemonte Orientale (UPO), Novara, Italy.
Department of Medicine, AOU Maggiore della Carità, Novara, Italy.
Gastroenterol Res Pract. 2020 Apr 24;2020:4216451. doi: 10.1155/2020/4216451. eCollection 2020.
A single-nucleotide polymorphism causing a C to G change in the gene (rs738409) is associated with disease severity and development of hepatocellular carcinoma (HCC) in nonalcoholic fatty liver disease; the insertion variant rs72613567:TA of the 17-hydroxysteroid dehydrogenase type 13 () mitigates this detrimental effect. Our aim was to evaluate if the same holds true in chronic hepatitis C virus infection (HCV). With a case control retrospective study design, we selected 110 patients who developed HCC on a background of HCV infection, matching each patient for sex and age (±30 months) to three HCV-infected, non-HCC patients. All participants underwent genotyping for and gene variants. Both univariate and multivariate analyses of risk factors for advanced disease and HCC were performed. Carriage of G∗ allele was associated with a trend of progressively more severe liver disease, from mild fibrosis to significant fibrosis, cirrhosis, and HCC ( = 0.007). When the status of these patients was taken into account, the abovementioned trend was strengthened among major allele homozygotes and completely blunted among carriers of the minor allele ( = 0.0003 and 0.953, respectively). In a conditional logistic regression model including diabetes and AST to platelet ratio index among predictor variables, the unfavourable genetic profile characterized by the coexistence of the minor allele and major allele (vs. all other possible combinations) was an independent risk factor for HCC (OR = 2.00, 95% CI: 1.23-3.26) together with a history of alcohol abuse. In conclusion, carriage of the combination minor allele and major allele may represent a risk factor for HCC among HCV-infected patients. The interplay between the two genes may explain some of the controversy on this topic and may be exploited to stratify HCC risk in hepatitis C.
一种导致基因中C到G变化的单核苷酸多态性（rs738409）与非酒精性脂肪性肝病的疾病严重程度和肝细胞癌（HCC）的发生相关；17β-羟类固醇脱氢酶13型（HSD17B13）的插入变体rs72613567:TA减轻了这种有害影响。我们的目的是评估在慢性丙型肝炎病毒（HCV）感染中是否也是如此。采用病例对照回顾性研究设计，我们选择了110例在HCV感染背景下发生HCC的患者，将每位患者按性别和年龄（±30个月）与3例HCV感染的非HCC患者进行匹配。所有参与者均对HSD17B13和PNPLA3基因变体进行基因分型。对晚期疾病和HCC的危险因素进行了单变量和多变量分析。携带PNPLA3 G*等位基因与肝病从轻度纤维化逐渐发展为显著纤维化、肝硬化和HCC的严重程度逐渐增加的趋势相关（P = 0.007）。当考虑这些患者的HSD17B13状态时，上述趋势在PNPLA3主要等位基因纯合子中得到加强，而在次要等位基因携带者中则完全消失（分别为P = 0.0003和0.953）。在一个条件逻辑回归模型中，预测变量包括糖尿病和AST与血小板比值指数，以PNPLA3次要等位基因和HSD17B13主要等位基因共存为特征的不利基因谱（与所有其他可能的组合相比）与酗酒史一起是HCC的独立危险因素（OR = 2.00，95%CI：1.23 - 3.26）。总之，PNPLA3次要等位基因和HSD17B13主要等位基因的组合携带可能代表HCV感染患者发生HCC的危险因素。这两个基因之间的相互作用可能解释了关于该主题的一些争议，并可能用于对丙型肝炎中的HCC风险进行分层。
