Gomaa Mostafa-Hedeab1,2, Dina Sabry3, Ghada Mostafa Abdelaziz4, Manal Ewaiss4,2, Nagla Adli4, Wael Fathy5. 1. Pharmacology department, Faculty of Medicine, Beni Suef University - Egypt. 2. Medical College, Al-Jouf University, Al-Jawf, Saudi Arabia. 3. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Cairo University, Cairo, Egypt. 4. Medical Biochemistry and Molecular Biology Department, Faculty of Medicine, Beni Suef University, Beni Suef, Egypt. 5. Tropical medicine Department, Faculty of Medicine, Beni Seuf University, Beni Suef, Egypt.
Abstract
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±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 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. CONCLUSION: 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.
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±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 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. CONCLUSION: 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.
Entities:
Keywords:
Egypt; Hepatitis B virus; PEGylated interferon; Vitamin D receptor polymorphism
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