This study aimed to assess whether the genetic polymorphisms rs10741657 G>A of CYP2R1, rs7041 G>T and rs4588 C>A of GC-globulin and rs10877012 G>T of CYP27B1, sequentially involved in the vitamin D pathway, could exert a cumulative effect in influencing the achievement of SVR in naïve patients with chronic hepatitis C treated with interferon plus ribavirin dual therapy. This evidence concerns the gene CYP27B1 and chronic hepatitis C virus infection.