Thesis (M.Sc.) - Cairo University -Faculty of Pharmacy - Department of Pharmaceutics

Background: Vitamin D binding protein (VDBP) has been identified as a potential modulator of immune response and is associated with clinical progression and adverse outcomes of many diseases. We assessed the influence of pretreatment 25-hydroxyvitamin D (vitamin D) levels and VDBP single nucleotide polymorphisms (SNPs), rs4588 (C>A) and rs7041 (G>T), on baseline clinical parameters and response to interferon/ribavirin therapy in chronic hepatitis C virus (CHC) patients in Egypt. Methods: Two single nucleotide polymorphisms in the VDBP gene, rs4588 and rs7041, were genotyped by polymerase chain reaction followed by restriction fragment length chain polymorphism in 112 treatment naïve hepatitis C patients and 50 healthy controls of matched age and gender. Patients were divided into two groups according to the number of major alleles in both loci studied: those with three or four major alleles (Wild diplotype [WT+]) and those with less than 3 major alleles (Non-Wild diplotype [WT-]). Vitamin D levels were assessed by ELISA. Hepatitis C virus (HCV) quantification by PCR was performed at baseline, weeks 12, 48, 72 after the start of therapy. METAVIR score was used to assess the degree of inflammatory liver activity and liver fibrosis. Results: Patients with VDBP WT+ diplotype had a statistically significant better chance of achieving a viral response at week 12, 48, and 72 (P values of 0.046, 0.034 and 0.029, respectively). Multivariate logistic regression identified VDBP WT+ diplotype as an independent predictor of sustained viral response (P= 0.013, OR= 4.716, CI= 1.389 {u2013} 16.013). Moreover, WT+ diplotype was associated with lower baseline viral load (P=0.016). Baseline vitamin D levels were not associated with baseline viral load or significant liver fibrosis. Vitamin D levels were also not associated with early, end of treatment, sustained viral response. The CC genotype of the rs4588 was associated with end of treatment response and sustained viral response. VDBP was associated with higher vitamin D levels. Moreover, the WT+ diplotype was associated with higher vitamin D levels. VDBP genotype, haplotype, diplotype did not differ among HCV patients and healthy controls

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