The role of vitamin D receptor polymorphisms in the course of chronic hepatitis C infection

Efthymios P. Tsounis; Evanthia Tourkochristou; Aggeliki Sapsani; Ioanna Aggeletopoulou; Theoni Lourida; Konstantinos Zisimopoulos; Theodoros Tzikopoulos; Georgia Diamantopoulou; Aggeliki Tsintoni; Konstantinos Thomopoulos; Athanasia Mouzaki; Christos Triantos

Authors Efthymios P. Tsounis, Evanthia Tourkochristou, Aggeliki Sapsani, Ioanna Aggeletopoulou, Theoni Lourida, Konstantinos Zisimopoulos, Theodoros Tzikopoulos, Georgia Diamantopoulou, Aggeliki Tsintoni, Konstantinos Thomopoulos, Athanasia Mouzaki, Christos Triantos.

Abstract

Background Vitamin D and its receptor (VDR) exert important immunoregulatory functions that contribute to liver homeostasis. The aim of this study was to investigate the influence of FokI, ApaI, BsmI and TaqI VDR polymorphisms on cirrhosis development and laboratory variables in patients with chronic hepatitis C (CHC).

Methods A total of 48 patients were enrolled in this retrospective, observational study and underwent genotype analysis; their medical records were examined to obtain relevant data.

Results The cumulative rate of progression to cirrhosis during the course of CHC was 31.3% after a median period of 11 years from diagnosis. Importantly, in multivariate analysis, FokI ff (adjusted hazard ratio [aHR] 13.6, 95% confidence interval [CI] 2.51-73.73; P=0.002) and ApaI aa (aHR 4.69, 95%CI 1.13-19.43; P=0.033) genotypes were independently associated with progression to cirrhosis. The presence of the aa genotype was also associated with higher liver stiffness measurements measured by transient elastography compared to the AA/Aa genotype (12.3kPa interquartile range [IQR] 9.6-17.3 vs. 7.1kPa IQR 5.6-11.1; P=0.012). In addition, higher HCV RNA and lower serum albumin levels were observed in patients with the tt genotype of the TaqI polymorphism compared to TT/Tt carriers, and in patients with the aa genotype compared to AA/Aa carriers. In haplotype analysis, no association was found between any haplotype and disease progression.

Conclusions In patients with CHC, laboratory parameters are influenced by VDR polymorphisms and the development of cirrhosis is related to homozygosity for the dominant trait of ApaI and FokI variants.

Keywords Chronic hepatitis C, vitamin D receptor, gene polymorphisms, liver cirrhosis, fibrosis progression

Ann Gastroenterol 2022; 35 (2): 203-212