Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis.

Multiple sclerosis (MS) is a complex disease of the central nervous system of unknown etiology. The human leukocyte antigen (HLA) locus on chromosome 6 confers a considerable part of the susceptibility to MS, and the most important factor is the class II allele HLA-DRB1*15:01. In addition, we and ot...

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Autores principales:	Jenny Link, Ingrid Kockum, Aslaug R Lorentzen, Benedicte A Lie, Elisabeth G Celius, Helga Westerlind, Marie Schaffer, Lars Alfredsson, Tomas Olsson, Boel Brynedal, Hanne F Harbo, Jan Hillert
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/ce8709991332409eae1ce68f6558e569
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spelling	oai:doaj.org-article:ce8709991332409eae1ce68f6558e5692021-11-18T07:19:26ZImportance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis.1932-620310.1371/journal.pone.0036779https://doaj.org/article/ce8709991332409eae1ce68f6558e5692012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22586495/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Multiple sclerosis (MS) is a complex disease of the central nervous system of unknown etiology. The human leukocyte antigen (HLA) locus on chromosome 6 confers a considerable part of the susceptibility to MS, and the most important factor is the class II allele HLA-DRB115:01. In addition, we and others have previously established a protective effect of HLA-A02. Here, we genotyped 1,784 patients and 1,660 healthy controls from Scandinavia for the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes and investigated their effects on MS risk by logistic regression. Several allele groups were found to exert effects independently of DRB115 and A02, in particular DRB101 (OR = 0.82, p = 0.034) and B12 (including B44/45, OR = 0.76, p = 0.0028), confirming previous reports. Furthermore, we observed interaction between allele groups: DRB115 and DRB101 (multiplicative: OR = 0.54, p = 0.0041; additive: AP = 0.47, p = 4 × 10(-06)), DRB115 and C12 (multiplicative: OR = 0.37, p = 0.00035; additive: AP = 0.58, p = 2.6 × 10(-05)), indicating that the effect size of these allele groups varies when taking DRB115 into account. Analysis of inferred haplotypes showed that almost all DRB115 bearing haplotypes were risk haplotypes, and that all A02 bearing haplotypes were protective as long as they did not carry DRB115. In contrast, we found one class I haplotype, carrying A02-C05-B12, which abolished the risk of DRB115. In conclusion, these results confirms a complex role of HLA class I and II genes that goes beyond DRB115 and A02, in particular by including all three classical HLA class I genes as well as functional interactions between DRB115 and several alleles of DRB1 and class I genes.Jenny LinkIngrid KockumAslaug R LorentzenBenedicte A LieElisabeth G CeliusHelga WesterlindMarie SchafferLars AlfredssonTomas OlssonBoel BrynedalHanne F HarboJan HillertPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 5, p e36779 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jenny Link Ingrid Kockum Aslaug R Lorentzen Benedicte A Lie Elisabeth G Celius Helga Westerlind Marie Schaffer Lars Alfredsson Tomas Olsson Boel Brynedal Hanne F Harbo Jan Hillert Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis.
description	Multiple sclerosis (MS) is a complex disease of the central nervous system of unknown etiology. The human leukocyte antigen (HLA) locus on chromosome 6 confers a considerable part of the susceptibility to MS, and the most important factor is the class II allele HLA-DRB115:01. In addition, we and others have previously established a protective effect of HLA-A02. Here, we genotyped 1,784 patients and 1,660 healthy controls from Scandinavia for the HLA-A, HLA-B, HLA-C and HLA-DRB1 genes and investigated their effects on MS risk by logistic regression. Several allele groups were found to exert effects independently of DRB115 and A02, in particular DRB101 (OR = 0.82, p = 0.034) and B12 (including B44/45, OR = 0.76, p = 0.0028), confirming previous reports. Furthermore, we observed interaction between allele groups: DRB115 and DRB101 (multiplicative: OR = 0.54, p = 0.0041; additive: AP = 0.47, p = 4 × 10(-06)), DRB115 and C12 (multiplicative: OR = 0.37, p = 0.00035; additive: AP = 0.58, p = 2.6 × 10(-05)), indicating that the effect size of these allele groups varies when taking DRB115 into account. Analysis of inferred haplotypes showed that almost all DRB115 bearing haplotypes were risk haplotypes, and that all A02 bearing haplotypes were protective as long as they did not carry DRB115. In contrast, we found one class I haplotype, carrying A02-C05-B12, which abolished the risk of DRB115. In conclusion, these results confirms a complex role of HLA class I and II genes that goes beyond DRB115 and A02, in particular by including all three classical HLA class I genes as well as functional interactions between DRB115 and several alleles of DRB1 and class I genes.
format	article
author	Jenny Link Ingrid Kockum Aslaug R Lorentzen Benedicte A Lie Elisabeth G Celius Helga Westerlind Marie Schaffer Lars Alfredsson Tomas Olsson Boel Brynedal Hanne F Harbo Jan Hillert
author_facet	Jenny Link Ingrid Kockum Aslaug R Lorentzen Benedicte A Lie Elisabeth G Celius Helga Westerlind Marie Schaffer Lars Alfredsson Tomas Olsson Boel Brynedal Hanne F Harbo Jan Hillert
author_sort	Jenny Link
title	Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis.
title_short	Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis.
title_full	Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis.
title_fullStr	Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis.
title_full_unstemmed	Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis.
title_sort	importance of human leukocyte antigen (hla) class i and ii alleles on the risk of multiple sclerosis.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/ce8709991332409eae1ce68f6558e569
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Importance of human leukocyte antigen (HLA) class I and II alleles on the risk of multiple sclerosis.

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