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dc.contributor.authorHaegert, D G
dc.contributor.authorSwift, F V
dc.contributor.authorBenedikz, J
dc.date.accessioned2011-03-08T11:18:14Z
dc.date.available2011-03-08T11:18:14Z
dc.date.issued1996-04
dc.date.submitted2011-03-08
dc.identifier.citationNeurology. 1996, 46(4):1107-11en
dc.identifier.issn0028-3878
dc.identifier.pmid8780100
dc.identifier.urihttp://hdl.handle.net/2336/123869
dc.descriptionTo access publisher full text version of this article. Please click on the hyperlink in Additional Links fielden
dc.description.abstractWe analyzed the association of HLA-DR and -DQ haplotypes and alleles with multiple sclerosis (MS) in 91 patients and 91 controls from Iceland using the relative predispositional effect method. The aim was to establish whether there is heterogeneity in HLA associations with MS, whether there are both predispositional and protective haplotypes, and whether sequence motifs also contribute to MS susceptibility. MS was positively associated with a DR2 haplotype (DRB5*0101-DQA1*0102-DQB1*0602), and empirical logistic analysis indicated that this haplotype is MS-associated because of a primary MS association with the DR2 allele. A DR13 haplotype (DRB1*1302-DQA1*0102-DQB1*0604) was negatively associated with MS, i.e., protective. Study of DR2-negative patients and controls confirmed this negative association and identified a second protective DR haplotype (DRB1*0701-DQA1*0201-DQB1*0201). Within these protective haplotypes in DR2-negative individuals, both DQA1 alleles and one DQB1 allele (*0604) were protective, but neither DR allele was protective, i.e., DQ loci may be more important than DR loci in encoding molecules protective against MS. Predispositional (Phe67) and protective (Ile67) DR beta sequence motifs were present in the total and DR2-negative patient and control groups. Since DQ but not DR alleles appear to be protective, DR beta Ile67 may confer additional protection against MS. Study of family-normal controls confirmed the MS association with the DR2 haplotype, and the transmission-disequilibrium test showed cosegregation and linkage of DR2 alleles and MS in families.
dc.language.isoenen
dc.publisherLippincott Williams & Wilkinsen
dc.relation.urlhttp://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00006114-199604000-00042&LSLINK=80&D=ovften
dc.subject.meshAllelesen
dc.subject.meshCase-Control Studiesen
dc.subject.meshGene Frequencyen
dc.subject.meshGenetic Linkageen
dc.subject.meshGenetic Predisposition to Diseaseen
dc.subject.meshGenotypeen
dc.subject.meshHLA-DQ Antigensen
dc.subject.meshHLA-DR2 Antigenen
dc.subject.meshHaplotypesen
dc.subject.meshHistocompatibility Antigens Class IIen
dc.subject.meshHumansen
dc.subject.meshIcelanden
dc.subject.meshMultiple Sclerosisen
dc.subject.meshReference Valuesen
dc.titleEvidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Icelanden
dc.typeArticleen
dc.contributor.departmentFaculty of Medicine, Memorial University of Newfoundland, St. John's, Canada.en
dc.identifier.journalNeurologyen
html.description.abstractWe analyzed the association of HLA-DR and -DQ haplotypes and alleles with multiple sclerosis (MS) in 91 patients and 91 controls from Iceland using the relative predispositional effect method. The aim was to establish whether there is heterogeneity in HLA associations with MS, whether there are both predispositional and protective haplotypes, and whether sequence motifs also contribute to MS susceptibility. MS was positively associated with a DR2 haplotype (DRB5*0101-DQA1*0102-DQB1*0602), and empirical logistic analysis indicated that this haplotype is MS-associated because of a primary MS association with the DR2 allele. A DR13 haplotype (DRB1*1302-DQA1*0102-DQB1*0604) was negatively associated with MS, i.e., protective. Study of DR2-negative patients and controls confirmed this negative association and identified a second protective DR haplotype (DRB1*0701-DQA1*0201-DQB1*0201). Within these protective haplotypes in DR2-negative individuals, both DQA1 alleles and one DQB1 allele (*0604) were protective, but neither DR allele was protective, i.e., DQ loci may be more important than DR loci in encoding molecules protective against MS. Predispositional (Phe67) and protective (Ile67) DR beta sequence motifs were present in the total and DR2-negative patient and control groups. Since DQ but not DR alleles appear to be protective, DR beta Ile67 may confer additional protection against MS. Study of family-normal controls confirmed the MS association with the DR2 haplotype, and the transmission-disequilibrium test showed cosegregation and linkage of DR2 alleles and MS in families.


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