| Literature DB >> 27001119 |
S Mahurkar1, M Moldovan2,3, V Suppiah1, M Sorosina4, F Clarelli4, G Liberatore4,5, S Malhotra6, X Montalban6, A Antigüedad7, M Krupa8, V G Jokubaitis9, F C McKay10, P N Gatt10, M J Fabis-Pedrini11, V Martinelli4, G Comi4,5, J Lechner-Scott12, A G Kermode11,13, M Slee8, B V Taylor14, K Vandenbroeck15,16,17, M Comabella6, F M Boneschi4,5, C King1.
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).Entities:
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Year: 2016 PMID： 27001119 DOI： 10.1038/tpj.2016.20
Source DB: PubMed Journal: Pharmacogenomics J ISSN： 1470-269X Impact factor: 3.550