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Multiple Sclerosis
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Article

Glypican 5 is an interferon-beta response gene: a replication study

MDC Cénit1, F Blanco-Kelly1, V de las Heras2, M Bartolomé2, EG de la Concha3, E Urcelay3, R Arroyo2, and A Martínez1*

1 Clinical Immunology Department, Hospital Clínico San Carlos, Madrid, Spain;
2 Multiple Sclerosis Unit, Hospital Clínico San Carlos, Madrid, Spain
3 Clinical Immunology Department, Hospital Clínico San Carlos, Madrid, Spain

* To whom correspondence should be addressed.


   Abstract

Background

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Interferon-beta is the most usual therapy in relapsing-remiting MS. However, approximately 50% of the treated patients do not respond adequately. Very recently, a genome-wide association study on interferon-beta pharmacogenetics has described polymorphisms at several genes that are associated with response to this treatment. Our aim is to replicate the results obtained at the two loci most strongly implicated in the response to interferon-beta treatment, HAPLN1 and GPC5.

Patients and methods

We performed a case–control study, analyzing 199 patients with MS treated with interferon-beta for at least 2 years and at least two documented relapses over the 2 years, previous to treatment onset. Responders had neither relapses nor increase in expanded disability status scale (EDSS) over the 2-year follow-up period, whereas nonresponders had at least two relapses or an increase in EDSS of at least 1 point. We studied three single-nucleotide polymorphisms (SNPs) in the GPC5 locus and three SNPs in the HAPLN1 locus by TaqMan technology. Allelic frequencies between responders and nonresponders were compared by a chi-square test.

Results

An association was found between GPC5 polymorphisms and the response to interferon-beta therapy in patients with MS, in agreement with earlier data (responder vs nonresponder patients: rs10492503, P = 0.0005). The other locus studied (HAPLN1) did not show association with treatment response to interferon-beta (all SNPs P > 0.05).

Conclusions

We confirm the association of polymorphisms within GPC5 with response to interferon-beta therapy in patients with MS.

Key Words: GPC5, HAPNL1, interferon-beta treatment, multiple sclerosis

First published on June 25, 2009, doi:10.1177/1352458509106509

Multiple Sclerosis 2009;15:913.

A more recent version of this article appeared on August 1, 2009


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NeurologyHome page
D. J. Pappas and J. R. Oksenberg
Multiple sclerosis pharmacogenomics: Maximizing efficacy of therapy
Neurology, January 5, 2010; 74(1_Supplement_1): S62 - S69.
[Abstract] [Full Text] [PDF]



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