Association Of 25-hydroxyvitamin D And Vitamin D Receptor Gene Polymorphisms With HCV Infection Susceptibility And Chronicity In A High-risk Chinese Han Population

Section 1Study on associations of plasma 25-hydroxyvitamin D levels with HCV infection susceptibility and chronicity in paid blood donors[Background] Between 1980s and 1990s, nonstandard commercial plasma donation was existed in some regions of Jiangsu province. These nonstandard behaviors caused the spread of some blood transmission diseases to blood donors, including hepatitis C virus. Most of the donors were women. Meanwhile they had never tested for HCV antibody and received antiviral therapy.[Objectives] To determine the associations of plasma 25-hydroxyvitamin D (25(OH)D) levels with HCV infection outcomes, liver function, and HCV RNA load in paid blood donors.[Methods] The plasma 25(OH)D levels and biochemical characteristics were examined in 99 HCV persistent infection cases,108 spontaneous clearance subjects and 115 healthy controls. Partial correlation analysis was used to evaluate the associations of plasma 25(OH)D levels with liver function and HCV viral load.[Results] There were statistically significant differences in the levels of plasma 25(OH)D, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) among the three groups (all P<0.05). The levels of plasma 25(OH)D in persistent HCV infection cases and spontaneous clearance subjects were respectively significantly lower than those in controls (all P＜0.05). Controlling for age, sex and body mass index (BMI), HCV viral load was negatively correlated with plasma 25(OH)D level (r=-0.139, P=0.016). No significant correlation was found between plasma 25(OH)D level and ALT and AST (all P>0.05)。[Conclusion] The low plasma 25(OH)D level may be involved in the development and pathogenesis of HCV infection. This implicates an important role for vitamin D level in immune regulation and HCV infection chronicity.Section 2Association of vitamin D receptor gene polymorphisms with HCV infection susceptibility and chronicity in a high-risk Chinese Han population[Background] Hepatitis C is a liver disease caused by the hepatitis C virus (HCV) that causes both acute and chronic infection. The majority (55%-85%) of infected persons will develop persistent (chronic) infection. The outcome and course of HCV infection are most likely determined by a complex interplay of viral and host factors. Vitamin D has been considered as an immune modulator, and exerted the effect through the vitamin D receptor (VDR). Therefore, the VDR gene polymorphism may be associated with the outcomes of HCV infection.[Objectives] We aim to investigate the associations of VDR gene polymorphisms with the susceptibility and the outcomes of HCV infection.[Methods] Three SNPs (rs2228570, rs757343 and rs739837) of VDR gene were genotyped by TaqMan assay among Chinese population, including 834 persistent infection subjects,538 HCV spontaneous clearance subjects and 1030 uninfected subjects. Binary logistic analyses were used to test the associations between these three SNPs and HCV infection outcomes.[Results] The results showed that subjects with the rs757343 A allele and rs739837 A allele had the significantly reduced risk of HCV susceptibility (dominant model: rs757343:adjusted OR=0.739,95%CI=0.612-0.891, P=1.535×10-3; rs739837: adjusted OR=0.699,95%CI=0.581-0.841,P=1.420×10-4). In the stratified analysis, the protection of rs757343 A allele and rs739837 A allele against HCV infection remained effective in young subjects (age≤50 years), male subjects, hemodialysis patients and drug users (all P<0.05). In addition, patients carrying rs739837 CA genotype were less prone to develop persistent infection (CA vs. CC:adjusted OR=0. 609,95%CI=0.416-0.892, P=0.011). A cumulative effect was observed between the joint effect of the two SNPs (rs757343 and rs739837) and HCV infection susceptibility (Ptrend=2.550×10-4). Furthermore, haplotype analysis (rs757343 and rs739837) indicated that compared with the most frequent haplotype GC, the haplotype AA (P=6.695×10-7) and GA (P=0.002) were correlated with a reduced risk of HCV infection susceptibility.[Conclusion] Our findings indicated that the polymorphisms of VDR gene (rs757343 and rs739837) are associated with the outcomes of HCV infection in a high-risk Chinese population.