Genome-wide pharmacogenomic analysis of the response to interferon beta therapy in multiple sclerosis

Archives of Neurology
Esther ByunJorge R Oksenberg

Abstract

To identify promising candidate genes linked to interindividual differences in the efficacy of interferon beta therapy. Recombinant interferon beta therapy is widely used to reduce disease activity in multiple sclerosis (MS). However, up to 50% of patients continue to have relapses and worsening disability despite therapy. We used a genome-wide pharmacogenomic approach to identify single-nucleotide polymorphism (SNP) allelic differences associated with interferon beta therapy response. Four collaborating centers in the Mediterranean Basin. Data Coordination Center at the University of California, San Francisco. A cohort of 206 patients with relapsing-remitting MS followed up prospectively for 2 years after initiation of treatment. DNA was pooled and hybridized to Affymetrix 100K GeneChips. Pooling schemes were designed to minimize confounding batch effects and increase confidence by technical replication. Single-nucleotide polymorphism detection. Comparison of allelic frequencies between good responders and nonresponders to interferon beta therapy. A multianalytical approach detected significant associations between several SNPs and treatment response, which were validated by individual DNA genotyping on an independent platform...Continue Reading

Citations

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