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ARTICLES: G. Dean, T. W. Yeo, A. Goris, C. J. Taylor, R. S. Goodman, M. Elian, A. Galea-Debono, A. Aquilina, A. Felice, M. Vella, S. Sawcer, and D.A.S. Compston HLA-DRB1 and multiple sclerosis in Malta Neurology 2008; 70: 101-105 [Abstract] [Full text] [PDF]

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HLA-DRB1 and multiple sclerosis in Malta

Sreeram V Ramagopalan, David A Dyment, A Dessa Sadovnick and George C Ebers   (12 March 2008)

HLA-DRB1 and multiple sclerosis in Malta 12 March 2008
Sreeram V Ramagopalan, University of Oxford University Dept. of Clinical Neurology, John Radcliffe Hospital, Oxford, OX3 9DU, United Kingdom, David A Dyment, A Dessa Sadovnick and George C Ebers Send Correspondence to journal: Re: HLA-DRB1 and multiple sclerosis in Malta george.ebers{at}clneuro.ox.ac.uk Sreeram V Ramagopalan, et al.	We read with interest the article by Dean et al. examining the association between the HLA-DRB1 gene and multiple sclerosis in Malta. [1] The authors observed a protective effect of the HLA-DRB1*11 allele in a study of 77 patients, but suggest that this may be a consequence of the over-representation of the MS risk allele, HLA-DRB1*15. Dean et al. assert that the protective effect of HLA-DRB1*11 that we observed in our study of over 4300 Canadian individuals, is also an artifact of the effect of HLA-DRB1*15. [2] We believe this is unfounded. The transmission probability of a given allele to MS patients depends on the other parental alleles. For example, parents heterozygous for HLA-DRB1*15/*X (where *X is any other allele) will necessarily undertransmit *X. This is taken into account by studying parents negative for alleles known to be transmission distorted and this was the approach employed by Dyment et al. HLA-DRB1*11 was significantly under-transmitted from HLA-DRB1*15 negative parents (Transmitted (TR) 81, Not-Transmitted (NT) 108, p=0.0495), first uncovering the protective nature of this allele. This was confirmed in our recent expanded study of over 7000 individuals (nearly 2500 MS patients) where HLA-DRB1*11 was again found to be significantly under transmitted from HLA-DRB1*15 negative parents (TR=157, NT=213, p=0.0036). [3] There can have been surely no doubt that HLA-DRB1*11 protected against MS prior to the Malta study. References 1. Dean G, Yeo TW, Goris A, et al. HLA-DRB1 and multiple sclerosis in Malta. Neurology 2007. 2. Dyment DA, Herrera BM, Cader MZ, et al. Complex interactions among MHC haplotypes in multiple sclerosis: susceptibility and resistance. Hum Mol Genet 2005;14:2019-2026. 3. Ramagopalan SV, Morris AP, Dyment DA, et al. The Inheritance of Resistance Alleles in Multiple Sclerosis. PLoS Genet 2007;3:e150. Disclosure: The authors report no conflicts of interest. The authors of the article had the opportunity to respond but declined.