Effect of a genetic variant associated with Multiple Sclerosis mirrors response to anti-TNF therapy
Though anti-TNF therapy can be effective in the treatment of many auto-immune diseases including Rheumatoid Arthritis (RA), drugs that block TNF can promote or exacerbate Multiple Sclerosis (MS).
A genetic variant (rs1800693) within the TNFRSF1A gene has been identified in multiple GWAS as being associated with MS but not associated with other auto-immune diseases, such as RA and Chrohn's disease. New findings show that allele G of rs1800693 (the risk allele for MS) alters exon splicing and results in a novel soluble TNFR1 protein that antagonizes TNF, mimicking the effect of anti-TNF therapeutics.
Therefore, disease-associated genetic variants identified in GWAS may provide insight into mechanisms behind drugs that cause adverse effects associated with inducing or exacerbating disease symptoms, and may help inform treatment choice for common multifactorial diseases.
Read the article in Nature Letters:
TNF receptor 1 genetic risk mirrors outcome of anti-TNF therapy in multiple sclerosisGregory, A.P. et al, Nature, Published online 08 July 2012
Find out more about the pharmacogenetics of anti-TNF therapies:
- Variants within the TNF gene have been associated with response to anti-TNF therapy.
- Genetic variants have been associated with response to infliximab, adalimumab, and etanercept.
- View a Clinical Annotation relevant to anti-TNF therapy response.
abbreviations
GWAS = genome-wide association studyMS = Multiple Sclerosis
RA = Rheumatoid Arthritis
TNF = tumor necrosis factor
TNFR1 = tumor necrosis factor binding protein 1TNFRSF1A = tumor necrosis factor receptor superfamily, member 1A