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

Citation

Mahurkar, S and Moldovan, M and Suppiah, V and Sorosina, M and Clarelli, F and Liberatore, G and Malhotra, S and Montalban, X and Antiguedad, A and Krupa, M and Jokubaitis, VG and McKay, FC and Gatt, PN and Fabis-Pedrini, MJ and Martinelli, V and Comi, G and Lechner-Scott, J and Kermode, AG and Slee, M and Taylor, BV and Vandenbroeck, K and Comabella, M and Boneschi, FM and King, C and The Australian and New Zealand Multiple Sclerosis Genetics Consortium (ANZgene), Response to interferon-beta treatment in multiple sclerosis patients: a genome-wide association study, Pharmacogenomics Journal, 17 pp. 312-318. ISSN 1470-269X (2017) [Refereed Article]

Copyright Statement

Copyright 2016 Macmillan Publishers Limited

DOI: doi:10.1038/tpj.2016.20

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).

Item Details

Item Type:Refereed Article
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Central Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:Taylor, BV (Professor Bruce Taylor)
ID Code:111297
Year Published:2017 (online first 2016)
Deposited By:Menzies Institute for Medical Research
Deposited On:2016-09-07
Last Modified:2017-11-29
Downloads:0

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