Tumor necrosis factor polymorphism in multiple sclerosis: no additional association independent of HLA.

In order to investigate whether genes coding for tumor necrosis factors (TNF) contribute to the pathogenesis of multiple sclerosis (MS) and also whether they have a non-random association with the MS associated HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotype, 40 MS patients and their parents were characterized at four polymorphic loci in the region of the TNF genes: a NcoI RFLP and three microsatellites. We were able to determine the parental haplotypes and used those which were not transmitted to the proband as controls. Fifty percent of the HLA-DRB1*1501-DQA1*0102-DQB1*0602 haplotypes carried the TNFc1-n2-a11-b4 allelic combination in both the patient and the control groups. However, there was no association of any of these TNF polymorphisms with MS, independent of that already described for the class II region. This, with the lack of association of DP alleles with MS, effectively marks the boundaries of the MS associated haplotype.