OAS1: a multiple sclerosis susceptibility gene that influences disease severity.

Hdl Handle:
http://hdl.handle.net/10147/207667
Title:
OAS1: a multiple sclerosis susceptibility gene that influences disease severity.
Authors:
O'Brien, M; Lonergan, R; Costelloe, L; O'Rourke, K; Fletcher, J M; Kinsella, K; Sweeney, C; Antonelli, G; Mills, K H; O'Farrelly, C; Hutchinson, M; Tubridy, N
Affiliation:
Education & Research Centre, St. Vincent's University Hospital, Elm Park, Dublin , 4, Ireland. margaretobrien@physicians.ie
Citation:
Neurology. 2010 Aug 3;75(5):411-8.
Journal:
Neurology
Issue Date:
1-Feb-2012
URI:
http://hdl.handle.net/10147/207667
DOI:
10.1212/WNL.0b013e3181ebdd2b
PubMed ID:
20679634
Abstract:
BACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.
Language:
eng
MeSH:
2',5'-Oligoadenylate Synthetase/*genetics; Adolescent; Adult; Aged; Aged, 80 and over; Child; Cohort Studies; Female; *Genetic Predisposition to Disease; Genotype; Humans; Immunologic Factors/therapeutic use; Interferon-beta/therapeutic use; Male; Middle Aged; Multiple Sclerosis/drug therapy/*genetics; Multiple Sclerosis, Relapsing-Remitting/drug therapy/*genetics; *Polymorphism, Single Nucleotide; Severity of Illness Index; Young Adult
ISSN:
1526-632X (Electronic); 0028-3878 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorO'Brien, Men_GB
dc.contributor.authorLonergan, Ren_GB
dc.contributor.authorCostelloe, Len_GB
dc.contributor.authorO'Rourke, Ken_GB
dc.contributor.authorFletcher, J Men_GB
dc.contributor.authorKinsella, Ken_GB
dc.contributor.authorSweeney, Cen_GB
dc.contributor.authorAntonelli, Gen_GB
dc.contributor.authorMills, K Hen_GB
dc.contributor.authorO'Farrelly, Cen_GB
dc.contributor.authorHutchinson, Men_GB
dc.contributor.authorTubridy, Nen_GB
dc.date.accessioned2012-02-01T10:34:25Z-
dc.date.available2012-02-01T10:34:25Z-
dc.date.issued2012-02-01T10:34:25Z-
dc.identifier.citationNeurology. 2010 Aug 3;75(5):411-8.en_GB
dc.identifier.issn1526-632X (Electronic)en_GB
dc.identifier.issn0028-3878 (Linking)en_GB
dc.identifier.pmid20679634en_GB
dc.identifier.doi10.1212/WNL.0b013e3181ebdd2ben_GB
dc.identifier.urihttp://hdl.handle.net/10147/207667-
dc.description.abstractBACKGROUND: Type 1 interferons upregulate oligoadenylate synthetase 1 (OAS1). A single nucleotide polymorphism (SNP) in exon 7 of OAS1 results in differential RNAseL enzyme activity, the A allele coding for a truncated form with low activity and the G conferring high activity. We hypothesized that OAS1 genotypes would influence both susceptibility to multiple sclerosis (MS) and disease activity with the AA genotype being overrepresented and the GG genotype underrepresented in relapsing-remitting MS (RRMS) with increased disease activity. METHODS: We examined OAS1 genotype distribution in 401 patients with MS, 394 healthy controls, and 178 patients with RRMS receiving interferon-beta (IFNbeta) assessed as 1) having no or minimal disease activity on IFNbeta, 2) having disease activity despite IFNbeta, and 3) 65 patients with RRMS with highly active disease. RESULTS: The OAS1 genotype distribution differed between patients with MS and controls (p = 0.000003), with lower frequency of GG homozygotes in patients with MS (6%) compared with controls (17%). In relation to disease severity, 34 (32%) patients with no or minimal disease activity on IFNbeta had the AA and 8 (8%) the GG genotype; of patients with disease activity despite IFNbeta, 27 (51%) were AA, while only 1 (2%) was GG (p = 0.03). Median time to first relapse on IFNbeta was 24 months in patients with RRMS with AA genotype and 33 months with AG or GG genotype (p = 0.04). The GG genotype was absent in 65 patients with highly active RRMS (p = 0.03). CONCLUSIONS: A functional OAS1 SNP, AA genotype, confers susceptibility to MS and the GG genotype may protect against increased disease activity.en_GB
dc.language.isoengen_GB
dc.subject.mesh2',5'-Oligoadenylate Synthetase/*geneticsen_GB
dc.subject.meshAdolescenten_GB
dc.subject.meshAdulten_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshChilden_GB
dc.subject.meshCohort Studiesen_GB
dc.subject.meshFemaleen_GB
dc.subject.mesh*Genetic Predisposition to Diseaseen_GB
dc.subject.meshGenotypeen_GB
dc.subject.meshHumansen_GB
dc.subject.meshImmunologic Factors/therapeutic useen_GB
dc.subject.meshInterferon-beta/therapeutic useen_GB
dc.subject.meshMaleen_GB
dc.subject.meshMiddle Ageden_GB
dc.subject.meshMultiple Sclerosis/drug therapy/*geneticsen_GB
dc.subject.meshMultiple Sclerosis, Relapsing-Remitting/drug therapy/*geneticsen_GB
dc.subject.mesh*Polymorphism, Single Nucleotideen_GB
dc.subject.meshSeverity of Illness Indexen_GB
dc.subject.meshYoung Adulten_GB
dc.titleOAS1: a multiple sclerosis susceptibility gene that influences disease severity.en_GB
dc.contributor.departmentEducation & Research Centre, St. Vincent's University Hospital, Elm Park, Dublin , 4, Ireland. margaretobrien@physicians.ieen_GB
dc.identifier.journalNeurologyen_GB
dc.description.provinceLeinster-

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