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

被引:39
作者
Cenit, M. D. C. [1 ]
Blanco-Kelly, F. [1 ]
de las Heras, V. [2 ]
Bartolome, M. [2 ]
de la Concha, E. G. [1 ]
Urcelay, E. [1 ]
Arroyo, R. [2 ]
Martinez, A. [1 ]
机构
[1] Hosp Clin San Carlos, Dept Clin Immunol, Madrid 28040, Spain
[2] Hosp Clin San Carlos, Multiple Sclerosis Unit, Madrid 28040, Spain
关键词
GPC5; HAPNL1; interferon-beta treatment; multiple sclerosis; MULTIPLE-SCLEROSIS; SUSCEPTIBILITY; THERAPY;
D O I
10.1177/1352458509106509
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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. Multiple Sclerosis 2009; 15: 913-917. http://msj.sagepub.com
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页码:913 / 917
页数:5
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