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. 2007 Jul 25;2(7):e664.
doi: 10.1371/journal.pone.0000664.

HLA-A confers an HLA-DRB1 independent influence on the risk of multiple sclerosis

Boel Brynedal  1 , Kristina Duvefelt, Gudrun Jonasdottir, Izaura M Roos, Eva Akesson, Juni Palmgren, Jan Hillert
Affiliations

HLA-A confers an HLA-DRB1 independent influence on the risk of multiple sclerosis

Boel Brynedal et al. PLoS One. .

Abstract

A recent high-density linkage screen confirmed that the HLA complex contains the strongest genetic factor for the risk of multiple sclerosis (MS). In parallel, a linkage disequilibrium analysis using 650 single nucleotide polymorphisms (SNP) markers of the HLA complex mapped the entire genetic effect to the HLA-DR-DQ subregion, reflected by the well-established risk haplotype HLA-DRB1*15,DQB1*06. Contrary to this, in a cohort of 1,084 MS patients and 1,347 controls, we show that the HLA-A gene confers an HLA-DRB1 independent influence on the risk of MS (P = 8.4x10(-10)). This supports the opposing view, that genes in the HLA class I region indeed exert an additional influence on the risk of MS, and confirms that the class I allele HLA-A*02 is negatively associated with the risk of MS (OR = 0.63, P = 7x10(-12)) not explained by linkage disequilibrium with class II. The combination of HLA-A and HLA-DRB1 alleles, as represented by HLA-A*02 and HLA-DRB1*15, was found to influence the risk of MS 23-fold. These findings imply complex autoimmune mechanisms involving both the regulatory and the effector arms of the immune system in the triggering of MS.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Empirical odds ratios (ORs) for combinations of the HLA-DRB1*15 and HLA-A*02 alleles.
A genotype of two HLA-A*02 alleles but no HLA-DRB1*15 allele was used as baseline in the calculation of ORs. P values are reported above the bars.
See this image and copyright information in PMC

References

    1. Horton R, Wilming L, Rand V, Lovering RC, Bruford EA, et al. Gene map of the extended human MHC. Nat Rev Genet. 2004;5:889–899. - PubMed
    1. Jersild C, Fog T. Histocompatibility (HL-A) antigens associated with multiple sclerosis. Acta Neurol Scand Suppl. 1972;51:377. - PubMed
    1. Hillert J. Human leukocyte antigen studies in multiple sclerosis. Ann Neurol. 1994;(36 Suppl):S15–17. - PubMed
    1. Lincoln MR, Montpetit A, Cader MZ, Saarela J, Dyment DA, et al. A predominant role for the HLA class II region in the association of the MHC region with multiple sclerosis. Nat Genet. 2005;37:1108–1112. - PubMed
    1. Naito S, Namerow N, Mickey MR, Terasaki PI. Multiple sclerosis: association with HL-A3. Tissue Antigens. 1972;2:1–4. - PubMed

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