Pharmacogenomic study in patients with multiple sclerosis Responders and nonresponders to IFN-β

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  • dc.contributor.author Bustamante, Marta F.ca
  • dc.contributor.author Morcillo Suárez, Carlos, 1969-ca
  • dc.contributor.author Leyva, Lauraca
  • dc.contributor.author Fernández, Oscarca
  • dc.contributor.author Farré, Xavierca
  • dc.contributor.author Navarro i Cuartiellas, Arcadi, 1969-ca
  • dc.contributor.author Comabella López, Manuelca
  • dc.date.accessioned 2018-01-19T11:19:17Z
  • dc.date.available 2018-01-19T11:19:17Z
  • dc.date.issued 2015
  • dc.description.abstract OBJECTIVES: We aimed to investigate the association between polymorphisms located in type I interferon (IFN)-induced genes, genes belonging to the toll-like receptor (TLR) pathway, and genes encoding neurotransmitter receptors and the response to IFN-β treatment in patients with multiple sclerosis (MS). METHODS: In a first or screening phase of the study, 384 polymorphisms were genotyped in 830 patients with MS classified into IFN-β responders (n = 416) and nonresponders (n = 414) according to clinical criteria. In a second or validation phase, the most significant polymorphisms associated with IFN-β response were genotyped in an independent validation cohort of 555 patients with MS (281 IFN-β responders and 274 nonresponders). RESULTS: Seven single nucleotide polymorphisms (SNPs) were selected from the screening phase for further validation: rs832032 (GABRR3; p = 0.0006), rs6597 (STUB1; p = 0.019), rs3747517 (IFIH1; p = 0.010), rs2277302 (PELI3; p = 0.017), rs10958713 (IKBKB; p = 0.003), rs2834202 (IFNAR1; p = 0.030), and rs4422395 (CXCL1; p = 0.017). None of these SNPs were significantly associated with IFN-β response when genotyped in an independent cohort of patients. Combined analysis of these SNPs in all patients with MS (N = 1,385) revealed 2 polymorphisms associated with IFN-β response: rs2277302 (PELI3; p = 0.008) and rs832032 (GABRR3; p = 0.006). CONCLUSIONS: These findings do not support an association between polymorphisms located in genes related to the type I IFN or TLR pathways or genes encoding neurotransmitter receptors and the clinical response to IFN-β. Nevertheless, additional genetic and functional studies of PELI3 and GABRR3 are warranted.
  • dc.description.sponsorship SM is early stage researcher of the FP7 (2007-2013) Marie Curie Initial Training Network "UEPHA*MS" (2008-2012; Grant Agreement Number 212877). Spanish Ministry of Economy and Competitiveness, SAF/ 2012-34670, MS research, 2013-2015. Ministerio de Economía y Competitividad (MINECO) Convocatoria Proyectos de Investigación 2012 (Madrid, Spain); Funciones intracelulares de tipo-no-citoquina de las subunidades de la familia IL-12; SAF2012-32118. Dirección General de Investigación Científica y Técnica - DGICYT. Spanish Government (BFU2012-38236).
  • dc.format.mimetype application/pdfca
  • dc.identifier.citation Bustamante MF, Morcillo-Suárez C, Malhotra S, Rio J, Leyva L, Fernández O et al. Pharmacogenomic study in patients with multiple sclerosis Responders and nonresponders to IFN-β. Neurol Neuroimmunol Neuroinflamm. 2015 Sep 24;2(5):e154. DOI: 10.1212/NXI.0000000000000154
  • dc.identifier.doi http://dx.doi.org/10.1212/NXI.0000000000000154
  • dc.identifier.issn 2332-7812
  • dc.identifier.uri http://hdl.handle.net/10230/33696
  • dc.language.iso eng
  • dc.publisher Wolters Kluwer (LWW)ca
  • dc.relation.ispartof Neurol Neuroimmunol Neuroinflamm. 2015 Sep 24;2(5):e154
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/FP7/212877
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-34670
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/SAF2012-32118
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2012-38236
  • dc.rights © 2015 American Academy of Neurology. This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword Interferon-induced genes
  • dc.subject.keyword Toll-like receptor
  • dc.subject.keyword Multiple sclerosis
  • dc.title Pharmacogenomic study in patients with multiple sclerosis Responders and nonresponders to IFN-βca
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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