- Title
- Pharmacogenomic study in patients with multiple sclerosis: responders and nonresponders to IFN-ß
- Creator
- Bustamante, Marta F.; Morcillo-Suárez, Carlos; Sánchez, Antonio J.; Urcelay, Elena; Alvarez-Lafuente, Roberto; Villar, Lusia M.; Alvarez-Cermeño, Jose Carlos; Farré, Xavier; Lechner-Scott, Jeannette; Vandenbroeck, Koen; Rodríguez-Antigüedad, Alfredo; Drulovic, Jelena S.; Malhotra, Sunny; Martinelli Boneschi, Filippo; Chan, Andrew; Oksenberg, Jorge; Navarro, Arcadi; Montalban, Xavier; Comabella, Manuel; Rio, Jordi; Leyva, Laura; Fernández, Oscar; Zettl, Uwe K.; Killestein, Joep; Brassat, David; García-Merino, Juan Antonio
- Relation
- Neurology: Neuroimmunology & Neuroinflammation Vol. 2, Issue 5
- Publisher Link
- http://dx.doi.org/10.1212/nxi.0000000000000154
- Publisher
- Wolters Klumer Health
- Resource Type
- journal article
- Date
- 2015
- Description
- 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.
- Subject
- polymorphisms; type I interferon-induced genes; toll-like receptor pathway; neurotransmitter receptors; IFN-β treatment; multiple sclerosis
- Identifier
- http://hdl.handle.net/1959.13/1313844
- Identifier
- uon:22647
- Identifier
- ISSN:2332-7812
- Language
- eng
- Full Text
- Reviewed
- Hits: 38579
- Visitors: 39026
- Downloads: 552
| Thumbnail | File | Description | Size | Format | |||
|---|---|---|---|---|---|---|---|
| View Details Download | ATTACHMENT02 | Publisher version (open access) | 130 KB | Adobe Acrobat PDF | View Details Download |