TNF-alpha and -beta gene polymorphisms in multiple sclerosis: a highly significant role for determinants in the first intron of the TNF-beta gene.
Tumor necrosis factor (TNF)-alpha and TNF-beta 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-beta gene (TNF-beta(+252)) and two promoter-region polymorphisms of the TNF-alpha gene (TNF-alpha(-308) and TNF-alpha(-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-beta(+252) genotypes were significantly associated with MS: The frequency of TNF-beta 2,2 was increased (p = 0.00009) while the frequency of TNF-beta 1,2 was decreased (p = 0.0012) in MS patients as compared to controls. TNF-alpha genotypes were not associated with MS. These results suggest that the TNF-beta gene plays a significant role in the etiopathogenesis of MS.
Fernandes Filho
Jose Americo M
JA
Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
Vedeler
Christian A
CA
Myhr
Kjell-Morten
KM
Nyland
Harald
H
Pandey
Janardan P
JP
D006801:Humans; D007438:Introns; D008233:Lymphotoxin-alpha / Q000235:genetics*; D009103:Multiple Sclerosis / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D008233:Lymphotoxin-alpha; D014409:Tumor Necrosis Factor-alpha