We also assessed the role of polymorphisms in the interferon pathway given that IFN�� increases the expression of several genes involved in the immunological response to HCV [35]. IFN�� has a potent antiviral http://www.selleckchem.com/products/Bicalutamide(Casodex).html action that is exerted indirectly through a complex mechanism [36] in which the myxovirus resistance protein A (MxA), the oligoadenylate synthase 1 (OAS1) and the suppressor of cytokine signaling 3 (SOCS3) are involved [37]. The genes that encode for MxA, OAS1 and SOCS3 are polymorphic and it has been assessed whether polymorphism in these genes modulate the response to interferon in HCV monoinfected subjects [38], [39]. The SOCS3 ?487A allele increases SOCS3 expression and was associated with pegIFN�� and ribavirin HCV treatment failure [38].

Furthermore, carriage of the MxA ?88G>T allele, was associated with a better response of HCV to interferon and polymorphism located in OAS1 gene was shown to be associated with spontaneous HCV clearance [39]. Our data in the current study in HCV-HIV coinfected subjects indicates that MxA, OAS1 and SOCS3 SNPs are not associated with HCV treatment efficacy and therefore confirm the results of previous investigations [40]. A new finding from our study was the association of the SOCS3 rs4969170 polymorphism with HCV treatment-induced neutropenia and thrombocytopenia. Plausible biological explanation can be searched in the fact that in studies in knockout mice, SOCS3 has been shown to be implicated in both granulopoiesis [41] and thrombopoiesis [42]. CTLA4 is a polypeptide involved in the processing of antigens by T-cell lymphocytes and influences the response of HCV to interferon.

Three studies have assessed the relationship between the polymorphisms rs231776 (+49A>G) and rs5247909 (?318C>A) in the CTLA4 gene and HCV treatment response, either in HCV monoinfected patients [43], [44] and in HCV/HIV co-infected individuals [45]. Despite some discrepancies regarding the effect of gender or the type of interferon �� used, data from these studies were consistent with an association between the two polymorphsms assessed and SVR. This association was particularly robust in carriers of the +49 GG genotype [45]. Our data do not replicate this findings since we found no significant associations between polymorphism in the CTLA4 gene and SVR.

Reasons for discrepancy may be seek in the lower number of patients in our study compared with that of other investigations, which suggest underpower. Genuine population differences may offer an additional explanation. Polymorphism in the ITPA gene has been related with a benign erythrocyte enzymopathy, which is characterized by the accumulation of ITP in red cells. The affected patients may develop anemia when they are treated with purine analogues. Ribavirin is a purine Anacetrapib analogue and previous studies have shown that ITPA genetic variants leading to ITPA deficiency are associated with ribavirin-induced anemia in HCV-treated patients [46].