Tumor Necrosis Factor-Alpha Gene Polymorphisms in Children with Multiple Sclerosis

Tumor necrosis factor-α (TNF-α) is a cytokine implicated in the pathogenesis of infectious and autoimmune disorders including multiple sclerosis (MS). Childhood-onset MS presents some clinical and laboratory features differing from adult disease. We studied TNF-α - 238 G→A and - 308 G→A polymorphisms in 24 patients with childhood-onset MS using PCR-RFLP and compared them with healthy control subjects from the same population (n = 93). The genotypes and allele frequencies were not different between patient and control groups (p = 0.348, 95 %CI, 0.28 - 1.92, χ² = 0.10 and p = 0.797, 95 %CI, 0.312 - 2.285, χ² = 0.20 for - 238 and - 308 alleles, respectively). Although the size of the study group is small, these results do not support a role for TNF-α gene polymorphisms in susceptibility to MS in children.

Key words

TNF-α - Gene polymorphism - Multiple sclerosis

References

• 1 Bitsch A, Kuhlmann T, Da Costa C, Bunkowski S, Polak T, Bruck W. Tumour necrosis factor alpha mRNA expression in early multiple sclerosis lesions: correlation with demyelinating activity and oligodendrocyte pathology.  Glia. 2000;  29 366-375
• 2 Boiko A N, Guseva M E, Guseva M R, Boiko S Y, Sudomoina M A, Bikova O V, Maslova O I, Favorova O O, Gusev E I. Clinico-immunogenetic characteristics of multiple sclerosis with optic neuritis in children.  J Neurovirol. 2000;  6 (Suppl 2) S 152-155
• 3 De Jong B A, Schrijver H M, Huizinga T W, Bollen E LEM, Polman C H, Uitdehaag B MJ. et al . Innate production of interleukin-10 and tumor necrosis factor affects the risk of multiple sclerosis.  Ann Neurol. 2000;  48 641-646
• 4 Fernandez-Arquero M, Arroyo R, Rubio A, Martin C, Vigil P, Conejero L. et al . Primary association of a TNF gene polymorphism with susceptibility to multiple sclerosis.  Neurology. 1999;  53 1361-1363
• 6 Huizinga T WJ, Westendorp R GJ, Bollen E LEM, Keijsers V, Brinkman B M, Langermans J A. et al . TNF-α promoter polymorphisms, production and susceptibility to multiple sclerosis in different groups of patients.  J Neuroimmunol. 1997;  72 149-153
• 7 Maurer M, Kruse N, Giess R, Kyriallis K, Toyka K V, Rieckmann P. Gene polymorphism at position -308 of the tumor necrosis factor alpha promotor is not associated with disease progression in multiple sclerosis patients.  J Neurol. 1999;  246 949-954
• 8 McDonnell G V, Kirk C W, Middleton D, Droogan A G, Hawkins S A, Patterson C C, Graham C A. Genetic association studies of tumour necrosis factor alpha and beta and tumour necrosis factor receptor 1 and 2 polymorphisms across the clinical spectrum of multiple sclerosis.  J Neurol. 1999;  246 1051-1058
• 5 Selcen D, Anlar B, Renda Y. Multiple sclerosis in childhood: report of 16 cases.  Eur Neurol. 1996;  36 79-84
• 9 Weinshenker B G, Hebrink D, Wingerchuk D M, Klein C J, Atkinson E, O'Brien P C, McMurray C T. Genetic variants in the tumor necrosis factor receptor 1 gene in patients with MS.  Neurology. 1999;  22 1500-1503
• 10 Willer C J, Ebers G C. Susceptibility to multiple sclerosis: interplay between genes and environment.  Curr Opin Neurol. 2000;  13 241-247
• 11 Wilson A G, Symons J A, Mc Dowell T L, McDevitt H O, Duff G W. Effects of a polymorphism in the human tumor necrosis factor-α promoter on transcriptional activation.  Proc Natl Acad Sci USA. 1997;  94 3195-3199
• 12 Wingerchuk D, Liu Q, Sobell J, Sommer S, Weinshenker B G. A population-based case-control study of the tumor necrosis factor alpha-308 polymorphism in multiple sclerosis.  Neurology. 1997;  49 626-628