Variant rs4149584 (R92Q) of the TNFRSF1A gene in patients with familial multiple sclerosis

Abstract

Genomic studies have identified numerous genetic variants associated with sus-ceptibility to multiple sclerosis (MS); however, each one explains only a small percentage of therisk of developing the disease. These variants are located in genes involved in specific path-ways, which supports the hypothesis that the risk of developing MS may be linked to alterationsin these pathways, rather than in specific genes. We analyzed the role of the TNFRSF1A gene,which encodes one of the TNF- receptors involved in a signaling pathway previously linked toautoimmune disease.Methods: We included 138 individuals from 23 families including at least 2 members with MS,and analyzed the presence of exonic variants of TNFRSF1A through whole-exome sequencing.We also conducted a functional study to analyze the pathogenic mechanism of variant rs4149584(-g.6442643C > G, NM 001065.4:c.362 G > A, R92Q) by plasmid transfection into human oligo-dendroglioma (HOG) cells, which behave like oligodendrocyte lineage cells; protein labelingwas used to locate the protein within cells. We also analyzed the ability of transfected HOGcells to proliferate and differentiate into oligodendrocytes.