Association of Vitamin D Gene Polymorphisms With HCV Infection Outcome

Background: Vitamin D derivatives and their receptor (VDR) are immune-response modulators in many diseases including malignancies, metabolic conditions, and infections. We hypothesized that one or more variants of VDR single nucleotide polymorphisms (SNPs) are associated with hepatocellular carcinoma (HCC) in hepatitis C virus (HCV) cirrhotic patients. Materials and Methods: A total of 861 subjects were recruited and classified as spontaneous viral clearance (SVC, n = 127), chronic hepatic cirrhosis (CHC, n = 392), and HCC (n = 342). Standard routine laboratory tests were performed and clinical features noted. All individuals were genotyped for seven SNPs spanning the VDR using real-time PCR. Results: Genotype frequencies of SNPs rs7970376, rs11568820, rs4516035, rs2228570 (Fok1), rs1544410 (Bsm-1), and rs731236 (Taq1), but not rs739837, were variously altered in CHC and HCC compared with SVC, and in HCC compared to CHC (all p < 0.001). The most powerful was rs7970376, which brought an OR (95% CI) of 7.14 (4.64-10.98) for HCC compared to SVC (p = 0.001). The carriage of the AGTAC haplotype of five SNPs were linked to CHC compared to SVC at OR 2.88 [95% CI 1.2-6.9] (p = 0.017) and with HCC compared to CHC at OR 1.54 [95% CI = 1.04-2.27 (p = 0.031). Conclusion: SNPs in VDR may have a potential role in the outcomes of patients with HCV infection. VDR SNPs; rs7970376, rs11568820, rs4516035, rs2228570 (Fok1), rs1544410 (Bsm-1), and rs731236 (Taq1) could be used as molecular markers to predict the risk of HCC.