학술논문
Response to interferon-beta treatment in multiple sclerosis patients: a genome-wide association study
Document Type
Academic Journal
Author
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; Fabis-Pedrini, M J; Martinelli, V; Comi, G; Lechner-Scott, J; Kermode, A G; Slee, M; Taylor, B V; Vandenbroeck, K; Comabella, M; Boneschi, F M; Australian, The; King, C
Source
The Pharmacogenomics Journal. Mar 24, 2016
Subject
Language
English
ISSN
1470-269X
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) and followed by variants in GAPVD1 (GTPase activating protein and VPS9 domains 1; combined P-value 5.83 × 10) and near ZNF697 (combined P-value 8.15 × 10).