Response to interferon-beta treatment in multiple sclerosis patients: a genome-wide association study

S. Mahurkar, M. Moldovan, V. Suppiah, M. Sorosina, F. Clarelli, G. Liberatore, S. Malhotra, X. Montalban, A. Antigüedad, M. Krupa, V. G. Jokubaitis, F.C. Mckay, P.N. Gatt, Marzena Pedrini, V. Martinelli, G. Comi, Jeannette Lechner-Scott, Allan Kermode, Mark Slee, B. V. TaylorK. Vandenbroeck, M. Comabella, F. M. Boneschi, C. King, The Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene)

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14 Citations (Scopus)

Abstract

Up to 50% of multiple sclerosis (MS) patients do not respond to interferon-beta (IFN-β) treatment and determination of response requires lengthy clinical follow-up of up to 2 years. Response predictive genetic markers would significantly improve disease management. We aimed to identify IFN-β treatment response genetic marker(s) by performing a two-stage genome-wide association study (GWAS). The GWAS was carried out using data from 151 Australian MS patients from the ANZgene/WTCCC2 MS susceptibility GWAS (responder (R)=51, intermediate responders=24 and non-responders (NR)=76). Of the single-nucleotide polymorphisms (SNP) that were validated in an independent group of 479 IFN-β-treated MS patients from Australia, Spain and Italy (R=273 and NR=206), eight showed evidence of association with treatment response. Among the replicated associations, the strongest was observed for FHIT (Fragile Histidine Triad; combined P-value 6.74 × 10- 6) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10-5) and near ZNF697 (combined P-value 8.15 × 10-5).The Pharmacogenomics Journal advance online publication, 22 March 2016; doi:10.1038/tpj.2016.20.

Original languageEnglish
Pages (from-to)312-318
JournalPharmacogenomics Journal
DOIs
Publication statusPublished - 22 Mar 2016

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    Mahurkar, S., Moldovan, M., Suppiah, V., Sorosina, M., Clarelli, F., Liberatore, G., Malhotra, S., Montalban, X., Antigüedad, A., Krupa, M., Jokubaitis, V. G., Mckay, F. C., Gatt, P. N., Pedrini, M., Martinelli, V., Comi, G., Lechner-Scott, J., Kermode, A., Slee, M., ... The Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene) (2016). Response to interferon-beta treatment in multiple sclerosis patients: a genome-wide association study. Pharmacogenomics Journal, 312-318. https://doi.org/10.1038/tpj.2016.20