Association of vitamin D binding protein polymorphisms with response to therapy in Egyptian chronic hepatitis C patients

Abstract

Introduction: Vitamin D binding protein (VDBP) is a potential modulator of immune response and is associated with clinical progression of many diseases. Our aim was to assess influence of baseline 25-hydroxyvitamin D levels and VDBP single nucleotide polymorphisms (SNPs), rs4588 (C > A) and rs7041 (G > T), on baseline clinical parameters and response to interferon based therapy in chronic hepatitis C patients in Egypt. Methodology: Genotyping was performed by RFLP (Restriction Fragment Length Polymorphism) in 112 treatment naïve hepatitis C patients and 50 healthy controls. Vitamin D levels were assessed by ELISA. HCV RNA quantification was performed by PCR to assess therapy outcome. Results: Patients with VDBP WT+ diplotype (3 or 4 VDBP major alleles) had higher viral response rates at weeks 12, 48, and 72 (p = 0.046, 0.034 and 0.029, respectively) and lower base line viral load (p = 0.016). Multivariate logistic regression identified VDBP WT+ diplotype as an independent predictor of sustained viral response (SVR; p = 0.014, RR = 4.716, 95% CI = 1.371 – 16.609). Interestingly, WT- diplotype (less than 3 VDBP major alleles) was associated with significant liver fibrosis (p = 0.045). Conclusions: VDBP WT+ diplotype is associated with lower baseline viral load and better therapy outcome in HCV treatment naïve patients. The rs4588 genotype is associated with SVR in the Egyptian population.