MHC2TA is associated with differential MHC molecule expression and susceptibility to rheumatoid arthritis, multiple sclerosis and myocardial infarction - PubMed (original) (raw)

doi: 10.1038/ng1544. Epub 2005 Apr 10.

Olle Lidman, Leonid Padyukov, Per Eriksson, Eva Akesson, Maja Jagodic, Anna Lobell, Mohsen Khademi, Ola Börjesson, Cecilia M Lindgren, Pia Lundman, Anthony J Brookes, Juha Kere, Holger Luthman, Lars Alfredsson, Jan Hillert, Lars Klareskog, Anders Hamsten, Fredrik Piehl, Tomas Olsson

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

Maria Swanberg et al. Nat Genet. 2005 May.

Abstract

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 --> 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-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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