Methylation of class II transactivator gene promoter IV is not associated with susceptibility to Multiple Sclerosis

Sreeram V Ramagopalan¹^,2 , David A Dyment¹^,2 , Katie M Morrison¹^,2 , Blanca M Herrera¹^,2 , Gabriele C DeLuca¹^,2 , Matthew R Lincoln¹^,2 , Sarah M Orton¹^,2 , Lahiru Handunnetthi¹^,2 , Michael J Chao¹^,2 , A Dessa Sadovnick³ and George C Ebers¹^,2

¹Wellcome Trust Centre for Human Genetics, University of Oxford, Roosevelt Drive, Headington, Oxford, OX3 7BN, UK

²Department of Clinical Neurology, University of Oxford, Level 3, The West Wing, The John Radcliffe Hospital, Oxford, OX3 9DU, UK

³Department of Medical Genetics and Faculty of Medicine, Division of Neurology, University of British Columbia, G920, Detwiller Pavilion, VCHA – UBC Hospital, 2211 Wesbrook Mall, Vancouver, British Columbia, V6T 2B5, Canada

author email corresponding author email

BMC Medical Genetics 2008, 9:63doi:10.1186/1471-2350-9-63


Published:	7 July 2008

Abstract

Background

Multiple sclerosis (MS) is a complex trait in which alleles at or near the class II loci HLA-DRB1 and HLA-DQB1 contribute significantly to genetic risk. The MHC class II transactivator (MHC2TA) is the master controller of expression of class II genes, and methylation of the promoter of this gene has been previously been shown to alter its function. In this study we sought to assess whether or not methylation of the MHC2TA promoter pIV could contribute to MS disease aetiology.

Methods

In DNA from peripheral blood mononuclear cells from a sample of 50 monozygotic disease discordant MS twins the MHC2TA promoter IV was sequenced and analysed by methylation specific PCR.

Results

No methylation or sequence variation of the MHC2TA promoter pIV was found.

Conclusion

The results of this study cannot support the notion that methylation of the pIV promoter of MHC2TA contributes to MS disease risk, although tissue and timing specific epigenetic modifications cannot be ruled out.