Genetic variant of RXR involved in the vitamin D metabolic pathway was linked to HCV infection outcomes among a high-risk Chinese population.

Abstract

Genetic variation of related genes in Vitamin D (VD) metabolic pathway played an important role in antiviral immune response and chronic hepatitis C virus (HCV) infection. Retinoid X receptor (RXR) is one of the key genes in the metabolism pathway of VD. This study aims to investigate the effect of single nucleotide polymorphisms (SNPs) in RXR on the outcomes of HCV infection. Three SNPs (RXRɑ-rs4842194, rs1045570 and RXRβ-rs2076310) were genotyped using Sequenom MassARRAY platform in 515 spontaneous clearance subjects, 830 persistent infection subjects, and 1062 uninfected subjects. Multivariate stepwise regression analyss was used to identify the prediction factors for HCV infection outcomes. The USCS Brower and RNAfold web serves were performed to further explore the potential biological functions of positive SNPs. The results of logistic regression analysis after adjusting for age, gender and types of high-risk population showed that subjects with RXRβ rs2076310-T (recessive model: adjusted OR = 1.598, 95%CI = 1.126-2.267, P = 0.009; additive model: adjusted OR = 1.196, 95%CI = 1.011-1.416, P = 0.037) had a significantly increased possibility of HCV infection chronicity. Rs2076310, age, types of high-risk population and aspartate aminotransferase were independent predictors of chronic HCV infection (P < 0.05). And the area under the receiver operating characteristic curve of combined effects of these factors was 0.679. Bioinformatics analysis indicated that rs2076310 could affect the gene expression level by affecting the transcriptional regulatory activity of the corresponding gene region. These findings indicated that genetic variation of RXRβ was associated with the risk of HCV infection chronicity among a high-risk Chinese population.

• Authors: Ru Zhang, Zuqiang Fu, Haozhi Fan, Ting Tian, Mengping Wu, Chaonan Xie, Peng Huang, Rongbin Yu, Yun Zhang, Wei Zhang, Jie Wang
• Journal: Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases (Infect Genet Evol) Vol. 87 Pg. 104641 (01 2021) ISSN: 1567-7257 [Electronic] Netherlands
• PMID: 33246082 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Biomarkers
• Retinoid X Receptor alpha
• Vitamin D

Topics

• Adult
• Aged
• Aged, 80 and over
• Asian People (genetics)
• Biomarkers (metabolism)
• Case-Control Studies
• China
• Female
• Genetic Predisposition to Disease
• Genotype
• Haplotypes
• Hepatitis C, Chronic (complications, genetics, physiopathology)
• Humans
• Male
• Metabolic Networks and Pathways (genetics)
• Middle Aged
• Polymorphism, Single Nucleotide
• Retinoid X Receptor alpha (genetics)
• Risk Factors
• Vitamin D (genetics, metabolism)