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Article
Nature Genetics  37, 486 - 494 (2005)
Published online: 10 April 2005; | doi:10.1038/ng1544

MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction

Maria Swanberg1, 10, Olle Lidman1, 10, Leonid Padyukov2, Per Eriksson3, Eva Åkesson4, Maja Jagodic1, Anna Lobell1, Mohsen Khademi1, Ola Börjesson2, Cecilia M Lindgren5, Pia Lundman6, Anthony J Brookes7, Juha Kere5, Holger Luthman8, Lars Alfredsson9, Jan Hillert4, Lars Klareskog2, Anders Hamsten3, Fredrik Piehl1, 10 & Tomas Olsson1, 10

1  Department of Clinical Neuroscience, Neuroimmunology Unit, Karolinska Institutet, Stockholm, Sweden.

2  Department of Medicine, Rheumatology Unit, King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden.

3  Atherosclerosis Research Unit, King Gustaf V Research Institute, Karolinska Institutet, Stockholm, Sweden.

4  Department of Neurology, Neurotec, Karolinska Institutet, Huddinge, Sweden.

5  Department of Biosciences at Novum, Karolinska Institutet, Huddinge, Sweden.

6  Department of Medicine, Danderyd's Hospital, Stockholm, Sweden.

7  Center for Genomics and Bioinformatics, Karolinska Institutet, Stockholm, Sweden.

8  Lund University, Department of Clinical Sciences, Malmö, Sweden.

9  Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.

10  These authors contributed equally to the work.

Correspondence should be addressed to Tomas Olsson tomas.olsson@cmm.ki.se
Antigen presentation to T cells by MHC molecules is essential for adaptive immune responses. To determine the exact position of a gene affecting expression of MHC molecules, we finely mapped a previously defined rat quantitative trait locus regulating MHC class II on microglia in an advanced intercross line. We identified a small interval including the gene MHC class II transactivator (Mhc2ta) and, using a map over six inbred strains combined with gene sequencing and expression analysis, two conserved Mhc2ta haplotypes segregating with MHC class II levels. In humans, a −168A right arrow G polymorphism in the type III promoter of the MHC class II transactivator (MHC2TA) was associated with increased susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction, as well as lower expression of MHC2TA after stimulation of leukocytes with interferon-bold gamma. We conclude that polymorphisms in Mhc2ta and MHC2TA result in differential MHC molecule expression and are associated with susceptibility to common complex diseases with inflammatory components.

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Nature Genetics
ISSN: 1061-4036
EISSN: 1546-1718
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