Pharmacogenomic analysis of interferon receptor polymorphisms in multiple sclerosis

Multiple sclerosis (MS) is a common inflammatory disease of the central nervous system characterized by progressive neurological dysfunction. No curative therapy is currently available, and approximately 80-90% of afflicted individuals are ultimately disabled. Interferon beta (IFNbeta) has been shown to decrease clinical relapses, reduce brain disease activity, and possibly slow progression of disability. However, the overall effect of treatment is partial and a substantial number of patients are considered poor or nonresponders. For this report, we tested the pharmacogenomic effects of eight polymorphisms in the interferon receptor genes (IFNAR1 and IFNAR2) in a group of 147 patients undergoing open-label IFNbeta therapy. Overall, no significant differences in the distribution of responders and nonresponders, classified based on prospectively acquired primary and secondary clinical end points, were observed when stratified by any of the studied IFNAR gene polymorphisms. A trend detected with a single nucleotide polymorphism SNP 16469 (A/T) located at the third intron of the IFNAR1 gene, suggesting modest association with relapse-free status, will require confirmation in an independent data set. In addition, no significant association was observed of any of the IFNAR gene polymorphisms with susceptibility to MS, as studied by a family-based association analysis.