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, M. J. Fabis-Pedrini, V. Martinelli, G. Comi, J. Lechner-Scott, A. G. Kermode, M. 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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23 Citations (Scopus)


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 × 106) 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).

Original languageEnglish
Pages (from-to)312-318
Number of pages7
JournalPharmacogenomics Journal
Issue number4
Publication statusPublished or Issued - 1 Jul 2017

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmacology

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