Bainrauch Ana, Šisl Dino, Markotić Antonio, Ostojić Ana, Gašparov Slavko, Bralić Lang Valerija, Kovačić Nataša, Grčević Danka, Mrzljak Anna, Kelava Tomislav
Department of Internal Medicine, Merkur University Hospital, 10000 Zagreb, Croatia.
Laboratory for Molecular Immunology, Croatian Institute for Brain Research, University of Zagreb, 10000 Zagreb, Croatia.
J Clin Med. 2021 Oct 8;10(19):4621. doi: 10.3390/jcm10194621.
Alcoholic liver cirrhosis (ALC) is the most common indication for liver transplantation (LT) in Croatia and presents a risk factor for the development of hepatocellular carcinoma (HCC). However, genetic susceptibility has not yet been systematically studied. We aimed to investigate the contribution of the risk polymorphisms rs738409, rs4444903, rs58542926, rs1801133, previously identified in other populations and, additionally, the contribution of Notch-related polymorphisms ( rs3124591, rs1043996 and rs1044116, rs422951). The study included 401 patients. The ALC group consisted of 260 LT candidates, 128 of whom had histopathologically confirmed HCC, and 132 of whom were without HCC. The control group included 141 patients without liver disease. Genotyping was performed by PCR using Taqman assays. The patients' susceptibility to ALC was significantly associated with rs738409, rs58542926, and rs1043996 polymorphisms. These polymorphisms remained significantly associated with ALC occurrence in a logistic regression model, even after additional model adjustment for sex and age. Cirrhotic patients with the GG genotype demonstrated higher activity of ALT aminotransferases than patients with CC or CG genotypes. The susceptibility to the development of HCC in ALC was significantly associated with rs738409 and rs4444903 polymorphisms, and logistic regression confirmed these polymorphisms as independent predictors.
酒精性肝硬化（ALC）是克罗地亚肝移植（LT）最常见的适应症，也是肝细胞癌（HCC）发生的危险因素。然而，遗传易感性尚未得到系统研究。我们旨在研究先前在其他人群中确定的风险多态性rs738409、rs4444903、rs58542926、rs1801133的作用，此外，还研究Notch相关多态性（rs3124591、rs1043996和rs1044116、rs422951）的作用。该研究纳入了401名患者。ALC组由260名LT候选者组成，其中128例经组织病理学证实患有HCC，132例未患HCC。对照组包括141名无肝病的患者。使用Taqman分析通过PCR进行基因分型。患者对ALC的易感性与rs738409、rs58542926和rs1043996多态性显著相关。即使在对性别和年龄进行额外模型调整后，这些多态性在逻辑回归模型中仍与ALC的发生显著相关。GG基因型的肝硬化患者ALT转氨酶活性高于CC或CG基因型的患者。ALC中HCC发生的易感性与rs738409和rs4444903多态性显著相关，逻辑回归证实这些多态性为独立预测因子。
