Beka Angeliki Anna, Papadopoulos Vasileios, Mylopoulou Theodora, Panopoulou Maria, Karakasiliotis Ioannis, Mavromara Penelope, Mimidis Konstantinos, Veletza Stavroula
MSc, Democritus University of Thrace, Department of Molecular Biology and Genetics, Laboratory of Biochemistry and Molecular Virology, Dragana, 68100, Alexandroupolis, Greece.
MD, ENARGEIA Medical Ltd., Michael Karaoli 8 & Elpidos 6, 67131, Xanthi, Greece.
Germs. 2022 Sep 30;12(3):384-393. doi: 10.18683/germs.2022.1342. eCollection 2022 Sep.
Hepatitis C virus (HCV) infection is a prime cause of chronic hepatitis worldwide, that often silently progresses to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Notably, the majority of individuals infected with HCV develop symptoms at late stages, often associated with liver damage that cannot revert after virus clearance. Thus, current antiviral therapy alone is rather insufficient to eliminate the global burden of HCV in the near future.During the past few years, vitamin D deficiency as well as certain single nucleotide polymorphisms in the vitamin D receptor (VDR) gene have been associated with liver fibrosis. Therefore, the aim of the present study was to investigate the possible correlation between VDR polymorphisms ApaI (rs7975232) and TaqI (rs731236) and the fibrosis stage of patients with HCV infection from Thrace, Greece.
Eighty-one patients with HCV infection underwent transient elastography for the assessment of their fibrosis stage, and PCR-restriction fragment length polymorphism (RFLP) genotyping for VDR ApaI and TaqI polymorphisms. VDR genotypes were then statistically associated with the patients' fibrosis stage using ordinal regression models.
Non-cirrhotic stages were positively correlated with TaqI TT genotype (p=0.003) and negatively correlated with TaqI TC genotype (p=0.007). In the presence of Hardy-Weinberg equilibrium and linkage disequilibrium between the two VDR polymorphisms, mild fibrosis stages (F0-2) were correlated with ApaI/TaqI GG/TT (p=0.002) and TG/TT (p=0.008) genotypes, while cirrhotic stage F4 was associated with ApaI/TaqI TG/TC genotype (p=0.038).
TaqI TT and ApaI/TaqI GG/TT, TG/TT and TG/TC genotypes could be explored as prognostic genetic markers for fibrosis susceptibility in HCV patients.
丙型肝炎病毒（HCV）感染是全球慢性肝炎的主要病因，常常悄然进展为肝纤维化、肝硬化和肝细胞癌（HCC）。值得注意的是，大多数感染HCV的个体在晚期才出现症状，且往往与病毒清除后无法逆转的肝损伤相关。因此，仅靠目前的抗病毒治疗在不久的将来还不足以消除全球范围内的HCV负担。在过去几年中，维生素D缺乏以及维生素D受体（VDR）基因中的某些单核苷酸多态性与肝纤维化有关。因此，本研究的目的是调查希腊色雷斯地区HCV感染患者VDR基因多态性ApaI（rs7975232）和TaqI（rs731236）与纤维化阶段之间可能存在的相关性。
81例HCV感染患者接受了瞬时弹性成像以评估其纤维化阶段，并进行了VDR ApaI和TaqI多态性的聚合酶链反应-限制性片段长度多态性（PCR-RFLP）基因分型。然后使用有序回归模型将VDR基因型与患者的纤维化阶段进行统计学关联。
非肝硬化阶段与TaqI TT基因型呈正相关（p=0.003），与TaqI TC基因型呈负相关（p=0.007）。在两种VDR多态性处于哈迪-温伯格平衡和连锁不平衡的情况下，轻度纤维化阶段（F0-2）与ApaI/TaqI GG/TT（p=0.002）和TG/TT（p=0.008）基因型相关，而肝硬化阶段F4与ApaI/TaqI TG/TC基因型相关（p=0.038）。
TaqI TT以及ApaI/TaqI GG/TT、TG/TT和TG/TC基因型可作为HCV患者纤维化易感性的预后遗传标志物进行研究。
