Multiple sclerosis (MS) is an idiopathic autoimmune neurodegenerative disease in which dysregulation of the immune system causes myelin sheath degradation. Multiple sclerosis is characterised by plaques or lesions in the brain and spinal cord. The location and size of the lesions is unpredictable. Symptoms of Multiple Sclerosis include affected coordination, balance and vision and disturbances in the bowel, bladder and sexual organs. Disease onset is typically between the ages of 20 and 40. Women have a 2 -3 fold higher incidence of MS than men. The distribution of MS inversely parallels the global distribution of UV light, suggesting a role for vitamin D in the disease.
First degree relatives of patients with MS are generally at 20 – 40 times greater risk of developing the disease themselves, compared to the general population, showing that the disease has a large genetic component. Family studies, including monozygotic and dizygotic twin studies have shown that HLA-DRB1*15:01 on the HLA-DRB1*15:01, DQA1*01:02, DQB1*06:02 haplotype, is a disease susceptibility gene, accounting for up to 35% of the heritability of the disease. Homozygosity for this haplotype increases disease risk six fold. Linkage disequilibrium initially made it difficult to confirm disease association with HLA-DRB1*15:01 rather than HLA-DQB1*06:02 but studies of MS in Black populations have confirmed HLA-DR*15:01 as the susceptibility gene. A role for other HLA class I and II alleles has been indicated by a number of studies but the overall effect of these remain small compared to HLA-DRB1*15.
The exact mechanism by which HLA increases the susceptibility to MS is unknown. A recent finding of a vitamin D response element in the promoter region of HLA-DRB1, which is completely conserved in HLA-DRB1*15:01 together with evidence showing that vitamin D is significantly lower in MS patients is suggestive.
A number of genome wide association studies have indentified other candidate genes other than HLA, including IL-7 Receptor alpha and the IL-2 Receptor alpha genes as MS disease susceptibility loci.
The main value of genetic testing in MS is to provide insights into the mechanism of the disease, thereby potentially suggesting strategies for prevention and treatment, rather than as a diagnostic tool.
Do you or someone you know suffer from Multiple Sclerosis or are you a researcher working in this area? Please join the conversation. Leave a comment. Thanks.
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