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 status has been found to predict the rate of sustained viral response (SVR) 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 evaluate the interaction between vitamin D and GC polymorphisms in predicting SVR. Methods: One hundred eighty-seven HCV patients treated with standard of care therapy were evaluated. Genotyping for the IL-28B rs12979860 C/T, for GC rs7041 T/G and for GC rs4588 C/A polymorphisms was performed. Results: SVR was achieved by 120/187 patients; 45/103 of HCV genotype 1-4-5, 75/84 of 2-3. Eighty three (44.4%) patients 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 rate of 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), HCV RNA ≤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 vitamin D status and GC gene polymorphisms predicts SVR in difficult to treat HCV genotypes.