Clinical relevance and functional consequences of the TNFRSF1A multiple sclerosis locus



In this prospective study, the researchers collected data on 772 MS patients to look at the role of the MS susceptibility allele (rs1800693G) found in the TNFRSF1A locus on both disease course and response to treatment. Serum samples were collected to assess the effects of rs1800693G and another allele, R92Q, in immune function.

There was no evidence that rs1800693G    influenced clinical or radiographic markers of disease course and treatment response. While at the molecular level, this susceptibility allele generates an RNA isoform, TNFRSF1A Δ6, which lacks the transmembrane and cytoplasmic domains. rs1800693G seems to change the state of monocytes, which shows a more robust transcriptional response of CXCL10 and other genes in response to TNF-α. They found that the activation of the TNF- α pathway caused altered expression of six other MS susceptibility genes, which were not known to be responsive to TNF-α.

This study shows that the MS susceptibility gene-rs1800693G, affects the magnitude of monocyte responses to TNF-α stimulation.

Authors: Ottobini L, Frolich IY

Source: Neurology. 2013 Oct 30. [Epub ahead of print]

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