Impact of CYP2R1, CYP27A1 and CYP27B1 genetic polymorphisms controlling vitamin D metabolism on susceptibility to hepatitis C virus infection in a high-risk Chinese population
CYP27A1, CYP2R1 and CYP27B1 hydroxylases are involved in the synthesis of 1, 25-hydroxyvitamin D3, which plays a role in the immune regulation and pathogenesis of hepatitis C virus (HCV) infection. The aim of the present study was to investigate the relationships between polymorphisms in vitamin D pathway genes and HCV infection outcomes in a Chinese population. Nine single-nucleotide polymorphisms (SNPs) of CYP27A1, CYP2R1 and CYP27B1 were genotyped in a high-risk Chinese population. The distributions of these SNPs were compared among groups with different outcomes of HCV infection, including 863 cases of persistent HCV infection, 524 cases of spontaneous clearance, and 1079 uninfected controls. The results showed that the CYP2R1 rs12794714-G, rs10741657-A, rs1562902-C, and rs10766197-G alleles were significantly associated with increased susceptibility to HCV infection (all PFDR < 0.05, in additive/dominant models), and the combined effect of the four unfavorable alleles was related to an elevated risk of HCV infection in a locus-dosage manner (Ptrend = 0.008). Moreover, haplotype analysis suggested that, compared with the most frequent haplotype (Ars12794714Grs10741657Trs1562902Ars10766197), the haplotype containing four unfavorable alleles, GACG, was associated with a higher risk of HCV infection. The results of our study suggest that genetic variants in CYP2R1 may be biomarkers for predicting the susceptibility to HCV infection in the Chinese population.
We thank all students, doctors and nurses who have worked in this study. We also thank the staff from the Nanjing Compulsory Detoxification Center, the Jurong People’s Hospital, and the other hospitals for organization of the field investigation and detection of serological samples. This research would not have been possible without the consent and help of the participants. The current study was financially supported by the National Natural Science Foundation of China (Grant nos. 81473028, 81773499 and 81703273), the Natural Science Foundation of Jiangsu Province, China (Grant no. BK20181369 and BK20171054), the Qing Lan Project, and the Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD,  87).
JW designed and organized the study. JY, HF, TT, MW, C-NX and PH contributed to the planning, designing and analyses of the experiments, data collection and quality control. J-JY, HF and TT performed the statistical analysis. RY and YZ provided materials and analysis tools. JY, HF and JW wrote and critically revised the manuscript. All authors read and approved the final manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
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