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


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.
Cénit
M D C
MD
Clinical Immunology Department, Hospital Clínico San Carlos, Madrid, Spain.
Blanco-Kelly
F
F
de las Heras
V
V
Bartolomé
M
M
de la Concha
E G
EG
Urcelay
E
E
Arroyo
R
R
Martínez
A
A
D000328:Adult; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D004185:Disability Evaluation; D016326:Extracellular Matrix Proteins / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D053673:Glypicans / Q000235:genetics*; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology; D016017:Odds Ratio; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D011509:Proteoglycans / Q000235:genetics; D012008:Recurrence; D018570:Risk Assessment; D013030:Spain; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000099249:Proteoglycan Link Protein
D016326:Extracellular Matrix Proteins; D053673:Glypicans; D007155:Immunologic Factors; D000068556:Interferon beta-1a; D000068576:Interferon beta-1b; D016899:Interferon-beta; D011509:Proteoglycans; D000099249:Proteoglycan Link Protein; C106228:GPC5 protein, human