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 (۴۲.۳±۱۰.۷ years) on PEG-IFN α-۲a (۱۸۰ μg /kg for ۴۸ weeks) and one hundred control subjects (۳۷.۳ ±۱۲ 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 ۱۰۷۳۵۸۱۰), BsmI A>G (rs ۱۵۴۴۴۱۰), ApaI (rs۷۹۷۵۲۵۳), and TaqI C>T (rs ۷۳۱۲۳۶), were genotyped using real-time PCR. Results: Hepatitis B virus patients expressed significantly greater AST (p=< ۰.۰۰۰۰۱) and ALT (P=< ۰.۰۰۰۰۱), and significantly less vitamin D (P=۰.۰۱), 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 Taq۱ single nucleotide polymorphisms (SNP) showed greater response to PEG-IFN therapy than those with the FF (P=۰.۰۲ and P=۰.۰۰۰۲), Bb (P=۰.۰۲۳), or Tt/tt alleles (P=۰.۰۱ and P=۰.۰۰۴ respectively). Logistic stepwise regression showed that HBV DNA (r: ۰.۹۱۰, P< .۰۰۰۰۱), FokI SNP polymorphism (r: ۰.۹۱۹, (P=۰.۰۳۷) and bAt haplotype (r: .۹۲۶, (P=۰.۰۴۳) 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.

Keywords:

Egypt , Hepatitis B virus , PEGylated interferon , Vitamin D receptor polymorphism.