MULTIPLE-SCLEROSIS - THE FREQUENCY OF ALLELIC FORMS OF TUMOR-NECROSIS-FACTOR AND LYMPHOTOXIN-ALPHA

The cytokines LTa and TNF have been implicated as major mediators of t issue injury in multiple sclerosis (MS). In this study we have assesse d the frequency of specific polymorphisms for these genes in MS (n = 5 3) and controls (n = 81) using a highly sensitive, two stage nested po lymerase chain reaction (PCR), with the second stage using mutation-sp ecific primers. Genomic DNA was extracted from blood cells and the res ults confirmed by direct dideoxy chain termination sequencing. The fre quency of the -308 G to A mutation in the TNF promoter region in norma l controls was 15% and in MS was 24%. For LTa gene the exon 3 polymorp hism allele A was detected in 36% of controls and 34% of the MS patien ts. In MS, the combined genotype TNF G + A and LTa C + C was present 6 times more frequently (12%) than in controls (2%), and patients with this genotype showed the highest EDSS scores. We found the TNF and LTa polymorphisms to occur independently from the HLA class Il DR2 allele distribution in MS. Whilst the G-A polymorphism in TNF gene promoter has been studied previously in MS, with conflicting results, this is t he first study that has addressed the exon 3 polymorphism in LTa in MS . The results indicate that this polymorphism is not linked with the h igher genetic predisposition for MS, but that combined TNF G + A and L Ta C + C genotype might contribute to development of the disease. (C) 1998 Elsevier Science B.V.