Bustamante, Marta F. (36647223700)Marta F. (36647223700)BustamanteMorcillo-Suárez, Carlos (24465436500)Carlos (24465436500)Morcillo-SuárezMalhotra, Sunny (50262475300)Sunny (50262475300)MalhotraRio, Jordi (7006734684)Jordi (7006734684)RioLeyva, Laura (6602303467)Laura (6602303467)LeyvaFernández, Oscar (7102560044)Oscar (7102560044)FernándezZettl, Uwe K. (7004582854)Uwe K. (7004582854)ZettlKillestein, Joep (7004423164)Joep (7004423164)KillesteinBrassat, David (55666405000)David (55666405000)BrassatGarcía-Merino, Juan Antonio (56154791100)Juan Antonio (56154791100)García-MerinoSánchez, Antonio J. (37665880200)Antonio J. (37665880200)SánchezUrcelay, Elena (10639601200)Elena (10639601200)UrcelayAlvarez-Lafuente, Roberto (13411081600)Roberto (13411081600)Alvarez-LafuenteVillar, Lusia M. (57210091951)Lusia M. (57210091951)VillarAlvarez-Cermeño, Jose Carlos (7004605927)Jose Carlos (7004605927)Alvarez-CermeñoFarré, Xavier (57192180234)Xavier (57192180234)FarréLechner-Scott, Jeannette (6603311349)Jeannette (6603311349)Lechner-ScottVandenbroeck, Koen (7003943780)Koen (7003943780)VandenbroeckRodríguez-Antigüedad, Alfredo (16417673500)Alfredo (16417673500)Rodríguez-AntigüedadDrulovic, Jelena S. (55886929900)Jelena S. (55886929900)DrulovicBoneschi, Filippo Martinelli (57202042750)Filippo Martinelli (57202042750)BoneschiChan, Andrew (7403168324)Andrew (7403168324)ChanOksenberg, Jorge (7005749242)Jorge (7005749242)OksenbergNavarro, Arcadi (35477108400)Arcadi (35477108400)NavarroMontalban, Xavier (7007177960)Xavier (7007177960)MontalbanComabella, Manuel (6701491362)Manuel (6701491362)Comabella2025-07-022025-07-022015https://doi.org/10.1212/NXI.0000000000000154https://www.scopus.com/inward/record.uri?eid=2-s2.0-85015273760&doi=10.1212%2fNXI.0000000000000154&partnerID=40&md5=e755c38cef7a764b9531ddc773af9afahttps://remedy.med.bg.ac.rs/handle/123456789/13540Objectives: 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; p5 0.010), rs2277302 (PELI3; p5 0.017), rs10958713 (IKBKB; p5 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. © 2015 American Academy of Neurology.