GENETIC-VARIATION IN THE TUMOR-NECROSIS-FACTOR-ALPHA GENE AND THE OUTCOME OF MULTIPLE-SCLEROSIS

The objective of this study was to determine whether sequence variatio n in the tumor necrosis factor alpha (TNF alpha) gene is associated wi th MS course and severity in Olmsted County, MN. The severity and temp oral course of MS are heterogeneous. Genetic factors may play a role i n determining the course of MS. TNF alpha expression is temporally ass ociated with exacerbations of MS and is increased in individuals with progressive disease. The entire TNF alpha gene was amplified by polyme rase chain reaction in 78 MS patients and in 39 patients with schizoph renia. Denaturation finger-printing, a modification of direct sequenci ng that detects virtually all genetic polymorphisms, was pet-formed fo r four regions spanning the functionally significant portions of the g ene, including the promoter region. Polymorphisms were confirmed by co mplete sequencing. The severity and temporal course of MS were compare d in those with wild-type versus variant alleles. Four sequence change s were detected, three of which occurred in MS patients. None occurred in a protein-encoding sequence. Neither of the two most common sequen ce variants were associated with disease severity or temporal course. Genetic variation of the TNF alpha gene is not associated with variati on in the course or long-term outcome of MS in this population-based s ample.