ANNUAL REVIEW master Final3a - St Vincent's University Hospital

St. Vincent’s Healthcare Group Limited - Annual Review 2007
Education & Research
Vitamin D is thought to mediate its immunomodulatory effects via the induction of tolerogenic dendritic
cells and regulatory T cells. IL-10 is also thought to play an important role in mediating the effects of
Vitamin D3. CD39, a recently described marker that identifies a subset of Treg, converts ATP to
adenosine, thereby mediating suppressive effects.
We plan to use CD39 as a marker of functional Treg and to correlate %CD39 expressing Treg with
vitamin D levels and other clinical parameters.
We will also measure the concentrations of IL-10 and other cytokines in the serum and correlate these
with Vitamin D levels.
d) To determine any genetic differences between people with MS in the Northwest and the South of
Ireland, and to compare with controls.
HLA DRB1*1501 typing and examination of vitamin D receptor (VDR) polymorphisms, which have
been associated with MS.
Genetic susceptibility to MS is implicated on the basis of classical family and monozygotic twin studies.
However the concordance rate in identical twins is only 25 to 30%, despite sharing 100% of DNA and
family environment. MS does not follow a particular pattern of inheritance and is probably a
multifactorial, polygenic disorder.
Several reviews have discussed linkage and association studies of the well known multiple sclerosis
candidate genes, the MHC, and specifically the HLA located at chromosome 6 (6p21), have long been
known to be associated with MS but exact location of the locus within the HLA complex is still largely
presumptive. In Northern European, and Ireland, carriage of DRB1*1501and the DQB2*0602 haplotype
of the HLA class 11 molecule is associated with increased MS risk.
Until recent association of IL2RA and IL7RA gene SNPs with MS, no definite links beyond MHC on
chromosome 6 had been established. However, this explains only a small proportion (less than 0.2%)
of the variance in the risk of the development of multiple sclerosis. As previously mentioned, vitamin D
receptor gene polymorphisms may also play a role in development of MS. It is likely that susceptibility
to MS probably consists of many risk alleles, each contributing a modest effect to overall risk.
e) To assess the needs of people with MS in Dublin, Wexford and Donegal
In collaboration with Dr. Malachi Mc Kenna, Consultant Endocrinologist; Dr. Barbara Murray, Principal
Biochemist; Dr. Jennifer Brady, Senior Biochemist, Metabolism Laboratory, SVUH; Dr. M.O’Brien, PhD
Genetics; Dr. J. Fletcher, Immunology, TCD; Dr. C. Dunne, IBTS; Dr. P. Fitzpatrick, UCD School of Public
Health /Pop. Science; Dr. Howard Johnson, National Population Health Directorate, HSE, Dr Steevens
Hospital; Dr. Peter Doran, CRC; MS Society
4. Oligoadenylate synthetase (OAS) in Multiple Sclerosis: not just a haplotype association.
MS is an autoimmune disease characterised by unregulated inflammation and subsequent
neurodegeneration. Type 1 Interferon (IFN) therapy is effective in some, but not all, patients. Type 1
interferons (endogenous and exogenous) exert anti-inflammatory effects by upregulating a number of
proteins, including those of the OAS family. A number of single-nucleotide polymorphisms (SNPs) of the
OAS 1 gene have been identified. A single nucleotide polymorphism (SNP) at exon 7 in the OAS 1 gene
influences OAS enzyme activity. Allele ‘G’ at exon 7 is associated with highest, and Allele ‘A’ lowest, OAS
activity.
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