Evidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Iceland
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field We 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 meth...
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ftlandspitaliuni:oai:www.hirsla.lsh.is:2336/123869 2023-05-15T16:47:30+02:00 Evidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Iceland Haegert, D G Swift, F V Benedikz, J Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada. 2011-03-08 http://hdl.handle.net/2336/123869 en eng Lippincott Williams & Wilkins http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00006114-199604000-00042&LSLINK=80&D=ovft Neurology. 1996, 46(4):1107-11 0028-3878 8780100 http://hdl.handle.net/2336/123869 Neurology Alleles Case-Control Studies Gene Frequency Genetic Linkage Genetic Predisposition to Disease Genotype HLA-DQ Antigens HLA-DR2 Antigen Haplotypes Histocompatibility Antigens Class II Humans Iceland Multiple Sclerosis Reference Values Article 2011 ftlandspitaliuni 2022-05-29T08:21:43Z To access publisher full text version of this article. Please click on the hyperlink in Additional Links field We 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. Article in Journal/Newspaper Iceland Hirsla - Landspítali University Hospital research archive |
institution |
Open Polar |
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Hirsla - Landspítali University Hospital research archive |
op_collection_id |
ftlandspitaliuni |
language |
English |
topic |
Alleles Case-Control Studies Gene Frequency Genetic Linkage Genetic Predisposition to Disease Genotype HLA-DQ Antigens HLA-DR2 Antigen Haplotypes Histocompatibility Antigens Class II Humans Iceland Multiple Sclerosis Reference Values |
spellingShingle |
Alleles Case-Control Studies Gene Frequency Genetic Linkage Genetic Predisposition to Disease Genotype HLA-DQ Antigens HLA-DR2 Antigen Haplotypes Histocompatibility Antigens Class II Humans Iceland Multiple Sclerosis Reference Values Haegert, D G Swift, F V Benedikz, J Evidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Iceland |
topic_facet |
Alleles Case-Control Studies Gene Frequency Genetic Linkage Genetic Predisposition to Disease Genotype HLA-DQ Antigens HLA-DR2 Antigen Haplotypes Histocompatibility Antigens Class II Humans Iceland Multiple Sclerosis Reference Values |
description |
To access publisher full text version of this article. Please click on the hyperlink in Additional Links field We 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. |
author2 |
Faculty of Medicine, Memorial University of Newfoundland, St. John's, Canada. |
format |
Article in Journal/Newspaper |
author |
Haegert, D G Swift, F V Benedikz, J |
author_facet |
Haegert, D G Swift, F V Benedikz, J |
author_sort |
Haegert, D G |
title |
Evidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Iceland |
title_short |
Evidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Iceland |
title_full |
Evidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Iceland |
title_fullStr |
Evidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Iceland |
title_full_unstemmed |
Evidence for a complex role of HLA class II genotypes in susceptibility to multiple sclerosis in Iceland |
title_sort |
evidence for a complex role of hla class ii genotypes in susceptibility to multiple sclerosis in iceland |
publisher |
Lippincott Williams & Wilkins |
publishDate |
2011 |
url |
http://hdl.handle.net/2336/123869 |
genre |
Iceland |
genre_facet |
Iceland |
op_relation |
http://ovidsp.ovid.com/ovidweb.cgi?T=JS&CSC=Y&NEWS=N&PAGE=fulltext&AN=00006114-199604000-00042&LSLINK=80&D=ovft Neurology. 1996, 46(4):1107-11 0028-3878 8780100 http://hdl.handle.net/2336/123869 Neurology |
_version_ |
1766037597950312448 |