Pharmacogenomic study in patients with multiple sclerosis: Responders and nonresponders to IFN-ß.
Neurol Neuroimmunol Neuroinflamm
; 2(5): e154, 2015 Oct.
Article
em En
| MEDLINE
| ID: mdl-26445728
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-ß 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-ß responders (n = 416) and nonresponders (n = 414) according to clinical criteria. In a second or validation phase, the most significant polymorphisms associated with IFN-ß response were genotyped in an independent validation cohort of 555 patients with MS (281 IFN-ß 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-ß 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-ß 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-ß. Nevertheless, additional genetic and functional studies of PELI3 and GABRR3 are warranted.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article