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Binder comment

Posted by kclarke on 23 Aug 2009 at 22:41 GMT

I do not profess to be an expert in the field but it seems to me that the comment by Dr Binder that "most of the DRB1 alleles carry the above VDRE
sequence motif and most of them are not associated with MS, it is not clear to us how vitamin D deficiency and the HLA-DRB1(*1501) promoter
contribute risk to one specific autoimmune disease such as MS." is missing the wood from the trees as it were.
Firstly, DR15 increases MS risk (and not other diseases). 60% of MS patients have this variant. Thus, it is DR15 that is important to MS.
Anything that influences DR15 is therefore of potential importance. The fact that a strongly suggested environmental factor for the disease influences
the main gene in MS is therefore IMPORTANT.
The argument that vitamin D might also influence other variants of this gene DOES NOT detract away from a role of vitamin D in regulating DR15.
Dr Binder's comment seems to muddy the waters on this front.
This paper by the team of George Ebers (who has over 200 papers on pubmed on MS, compared to 0 by Dr Binder), as I understand it,
does not say it is the gene promoter that contributes to MS risk, rather the influence of vitamin D on DR15 which may be important in MS.
Secondly, even if vitamin D influences other DR variants, my understanding is that other DR variants are associated to MS.
Thus, this suggests even more of a role of vitamin D in MS. Assigning VDRE+ and VDRE- status using the data provided by Dr Binder to the alleles carried
by MS patients and controls as described by the International MS Genetics Consortium provides a VDRE+ allele frequency of 75% in MS patients,
compared to 64% in controls (p=9x10^-21).
I am no geneticist or statistician, but to me, the role of vitamin D in regulating other DR alleles is actually more interesting rather than less.

K Clarke,
MS Patient

No competing interests declared.
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