Influence of Vitamin D Receptor Gene Polymorphisms on Response to Pegylated Interferon in Chronic Hepatitis B Egyptian Patients

Background: We explored the effect of vitamin D receptor gene (VDR) polymorphisms in response to PEG-IFN treatment in Egyptian chronic hepatitis B (CHB) patients. Methods: Two hundred hepatitis B virus (HBV) patients (42.3&plusmn;10.7 years) on PEG-IFN &alpha;-2a (180 &mu;g /kg for 48 weeks) and one hundred control subjects (37.3 &plusmn;12 years) were enrolled in the study. Vitamin D levels and hepatitis B surface antigen (HBsAg) expression were assessed by ELISA. VDR polymorphisms FokI T>C (rs 10735810), BsmI A>G (rs 1544410), ApaI (rs7975253), and TaqI C>T (rs 731236), were genotyped using real-time PCR. Results: Hepatitis B virus patients expressed significantly greater AST (p=< 0.00001) and ALT (P=< 0.00001), and significantly less vitamin D (P=0.01), than control subjects. Patients with Ff or ff alleles of the FokI single-nucleotide polymorphism (SNP), bb alleles of BsmI SNP, or TT alleles of the Taq1 single nucleotide polymorphisms (SNP) showed greater response to PEG-IFN therapy than those with the FF (P=0.02 and P=0.0002), Bb (P=0.023), or Tt/tt alleles (P=0.01 and P=0.004 respectively). Logistic stepwise regression showed that HBV DNA (r: 0.910, P< .00001), FokI SNP polymorphism (r: 0.919, (P=0.037) and bAt haplotype (r: .926, (P=0.043) are independent factors that determine PEG-IFN treatment response in the HBV-infected patients. Conclusions: VDR gene polymorphisms may be used as treatment response predictors in HBV patients receiving PEG-IFN. FokI SNP and bAt haplotype are independent factors that that can be used to determine PEG-IFN treatment responses in HBV-infected patients.