CYP24A1 genetic variants in the vitamin D metabolic pathway are involved in the outcomes of hepatitis C virus infection among high-risk Chinese population.

Abstract

BACKGROUND AND AIMS:

It has been demonstrated that 1,25-hydroxyvitamin-D3-24-hydroxylase, encoded by CYP24A1 gene, is a key enzyme that neutralizes the active vitamin D3 metabolite 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] in response to hepatitis C virus (HCV) infection. This study aimed to investigate whether CYP24A1 genetic variation is associated with HCV infection outcomes.

METHODS:

848 HCV chronically infected subjects, 507 natural clearance subjects, and 1017 uninfected controls were enrolled. Nine single nucleotide polymorphisms (SNPs) in theCYP24A1 gene were genotyped using the Sequenom MassARRAY platform.

RESULTS:

After adjusting for age, gender, and routes of infection, logistic regression analyses showed that rs6013897-A was associated with an elevated risk of HCV infection (P<0.05). In addition, this study has also demonstrated that rs6068816-T significantly reduced the risk of chronic HCV infection, while rs3787557-C, rs6022999-G, and rs2248359-T significantly increased the risk of chronic HCV infection (all P<0.05). Haplotype analysis suggested that, compared to the most frequent Trs6068816Trs3787557Ars6022999Crs2248359 haplotype, the CTGT haplotype (adjusted OR=1.376, 95% CI=1.092-1.735, P=0.007) and CCAC haplotype (adjusted OR=1.483, 95% CI=1.139-1.929, P=0.003) were associated with an increased risk of chronic HCV infection.

CONCLUSION:

These findings indicate that SNPs in CYP24A1 gene may contribute to the risk of HCV infection and chronic HCV infection among a high-risk Chinese population.

• Authors: Hao-Zhi Fan, Ru Zhang, Ting Tian, Yu-Ling Zhong, Meng-Ping Wu, Chao-Nan Xie, Jing-Jing Yang, Peng Huang, Rong-Bin Yu, Yun Zhang, Jie Wang
• Journal: International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases (Int J Infect Dis) Vol. 84 Pg. 80-88 (Jul 2019) ISSN: 1878-3511 [Electronic] Canada
• PMID: 31075507 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.

Chemical References

• Vitamin D
• CYP24A1 protein, human
• Vitamin D3 24-Hydroxylase

Topics

• Adult
• Female
• Haplotypes
• Hepatitis C, Chronic (etiology, genetics)
• Humans
• Male
• Metabolic Networks and Pathways
• Middle Aged
• Polymorphism, Single Nucleotide
• Risk Factors
• Vitamin D (metabolism)
• Vitamin D3 24-Hydroxylase (genetics)