Possible Implication of GSTP1 and NQO1 Polymorphisms on Natalizumab Response in Multiple Sclerosis

Oxidative stress plays a pivotal role in the pathogenesis of multiple sclerosis (MS). Inactivating polymorphism of genes encoding detoxification enzymes, such as NQO1 and GSTP1 could influence susceptibility to MS. The monoclonal antibody natalizumab is an effective treatment in MS. Natalizumab's efficacy in MS patients with regard to NQO1 and GSTP1 genetic polymorphisms is investigated. 130 patients with definite MS according to the Mc Donald's criteria treated monthly with natalizumab were included in the study. MS patients were classified with regard to their clinical subtype, gender and clinical outcome after Natalizumab administration. GSTP1 and NQO1 genotyping was performed using Real-Time PCR and PCR-RFLP assays. Among our cohort of MS patients, 88.5% responded and 11.5% manifested clinical deterioration after natalizumab treatment. Statistical analysis revealed a significantly increased frequency of double NQO1 and GSTP1 mutant polymorphisms in non responders compared to the responders. Therefore, patients who carry the wild type genotype or only one polymorphism for either NQO1 or GSTP1 gene have possibly a better clinical outcome after the natalizumab therapy. Our findings indicate that antioxidant efficiency might reflect a better clinical outcome after natalizumab administration. Hence, oxidative stress reduction might be another mechanism through which natalizumab exerts its protective effect.