2026-04-17T20:19:51Zhttps://recercat.cat/oai/request
oai:recercat.cat:10230/336962025-12-13T21:22:23Zcom_2072_6col_2072_452952
RECERCAT author Bustamante, Marta F. author Morcillo Suárez, Carlos, 1969- author Leyva, Laura author Fernández, Oscar author Farré, Xavier author Navarro i Cuartiellas, Arcadi, 1969- author Comabella López, Manuel 2018-01-19T11:19:17Z2018-01-19T11:19:17Z2015 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.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). © 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. http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess Interferon-induced genes Toll-like receptor Multiple sclerosis Pharmacogenomic study in patients with multiple sclerosis Responders and nonresponders to IFN-β info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion