Interaction between vitamin D binding protein polymorphisms and vitamin D levels in the prediction of antiviral response in chronic hepatitis C.

Background and Aim: Vitamin D deficiency has been found to predict the unsuccessful achievement of sustained viral response (SVR) after anti-viral treatment in hepatitis C virus (HCV) difficult to treat genotypes. Vitamin D binding protein (GC) gene polymorphisms are known to influence vitamin D levels. This study was performed to ascertain whether the interaction between vitamin D levels and GC polymorphisms could enhance the prediction of SVR. Methods: One hundred eighty seven HCV patients of Caucasian ethnicity (l00 males, median age 46 years) were evaluated. All were treated with a combination therapy of PEG-interferon plus ribavirin. Basal vitamin D levels and HOMA score were determined. Genotyping for the IL-28B rs12979860 C/T, for GC rs7041 T/G and for GC rs4588 C/A polymorphisms was performed by RFLP assay. Results: SVR was achieved by 120/187 patients; 37/88 of HCV genotype 1, 43/48 of 2, 32/36 of 3, 8/15 of 4/5. One hundred four (55.6%) patients had normal (>20 ng/mL) vitamin D and 83 (44.4%) had vitamin D deficiency (≤20 ng/mL). GC genotype frequencies for the rs7041 G>T and rs4588 C>A polymorphisms were: G/G = 60 (32.1%), G/T = 89 (47.6%), T/T = 38 (20.3%) and C/C = 98 (52.4%), C/A = 76 (40.6%), A/A = 13 (7.0%). Patients were divided into those carrying 3/4 major alleles (WT+: G-C/G-C, G-C/T-C, G-C/G-A, N= 91) and the remaining (WT−: G-C/T-A, T-A/T-C, T-A/T-A, T-C/T-C, N= 96). Four groups were identified: A) vitamin D≤20 and WT−, B) vitamin D≤20 and WT+, C) vitamin D >20 and WT−, D) vitamin D >20 and WT+. In difficult to treat HCV genotypes a significant linear trend was observed in the proportion of patients achieving SVR: A) 6/22), B) 9/24, C) 12/29, D) 18/28, p = 0.009. A stepwise logistic regression, the achievement of SVR in difficult to treat genotypes was found to be independently associated with IL28B C/C genotype (O.R. 8.46, p < 0.001), vitamin D >20 ng/mL and GC WT+ (O.R. 3.96, p = 0.021), HCVRNA ≤550.000 I.U./mL (O.R. 4.55, p = 0.003) and cholesterol ≤200 mg/dL (O.R. 0.18, p = 0.013). Conclusions: The interaction between the carriage of the wild type allele for the GC rs7041 and rs4588 polymorphisms and normal vitamin D predicts the successful achievement of SVR in difficult to treat HCV genotypes.