Vitamin D Receptor BsmI and Vitamin D Binding Protein Polymorphisms associated with Hepatocellular Carcinoma Susceptibility in Cirrhotic HCV Patients

Abstract

Background: The severity of chronic hepatitis C and susceptibility to hepatocellular carcinoma (HCC) are currently associated with specific genetic variations within vitamin D receptor (VDR). This study aims to assess the association of VDR and vitamin D binding protein (DBP) gene polymorphisms with HCC susceptibility in Egyptian cirrhotic HCV patients. Methods: Single nucleotide polymorphisms (SNPs) in the VDR (rs2228570, rs3782905, rs11568820) and DBP rs7041 genes were genotyped using single-stranded polymorphism PCR (SSP-PCR) or restriction fragment length-PCR (RFLP-PCR) techniques. These SNPs genotypes, haplotypes and linkage disequilibrium analyses were examined in 299 Egyptian individuals (100 HCV-cirrhotic patients, 99 HCC- HCV patients, and 100 healthy controls). Logestic regression analysis was also applied to determine association with HCC progression risk. Result: The VDR rs2228570 CC genotype, VDR rs3782905 GC and CC genotypes, and DBP rs7041 GG genotype are significantly correlated with a higher risk of HCC. It is noteworthy that, VDR rs3782905 CC and DBP rs7041 TG genotypes are more associated with higher risk of HCV induced liver cirrhosis than with HCC progression in HCV infected patients. Furthermore, among patients, the relationship between these SNPs and smoking status, gender, and HCC susceptibility was reported. Conclusion: Among the four investigated SNPs, there is an association between VDR rs3782905 and DBP rs7041 and the HCC progression in Egyptian patients chronically infected with HCV. The combinations of these SNPs with smoking status and gender are statistically linked to a high risk of HCC. These results suggest that VDR polymorphisms may be potential determinants for HCC susceptibility in Egyptian HCV patients.