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Abstract
Tumor necrosis factor (TNF)- f and TNF- g are proinflammatory cytokines that have been implicated in the pathogenesis of several autoimmune diseases. The aim of this investigation was to determine whether a determinant in the first intron of the TNF- g gene (TNF- g +252 ) and two promoter-region polymorphisms of the TNF- f gene (TNF- f m 308 and TNF- f m 238 ) affect susceptibility to multiple sclerosis (MS). DNA samples from 133 Caucasian MS patients and 148 healthy controls from Norway were genotyped for several polymorphic determinants, using polymerase chain reaction-based restriction fragment length polymorphisms (PCR-RFLP) methods. TNF- g +252 genotypes were significantly associated with MS: The frequency of TNF- g 2,2 was increased ( p =0.00009) while the frequency of TNF- g 1,2 was decreased ( p =0.0012) in MS patients as compared to controls. TNF- f genotypes were not associated with MS. These results suggest that the TNF- g gene plays a significant role in the etiopathogenesis of MS.