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

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±10.7 years) on PEG-IFN α-2a (180 μg /kg for 48 weeks) and one hundred control subjects (37.3 ±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 realtime 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 singlenucleotide 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.