Evaluation of the Apo-I/Fas promoter Mva I polymorphism in multiple sclerosis

The pathogenesis of multiple sclerosis is under strong genetic control invo lving several or more genes each of modest effect Whilst the mechanisms und erlying the pathogenesis of MS remain unknown, it has been hypothesised tha t either decreased apoptosis of autoreactive T cells in the CNS, or increas ed apoptosis of oligodendrocytes may play on important role The Apo-1/Fas a ntigen (CD95), the gene for which is located in a chromosomal region showin g linkage in MS genome screens, is a critical inducer of apoptosis and stud ies have shown aberrant expression of this molecule in MS, correlating with a decrease in T cell apoptosis or increase in CNS tissue damage. This stud y investigated an Mva 1 polymorphism, in the Apo-1/Fas promoter region in a group of 124 Australian patients with relapsing-remitting MS and in 183 no rmal controls. Whilst there were increases in the Mva 1*2 allele in MS indi viduals overall (59% vs 52%, P not corrected=0.08), and in HLA-DRB1*1501 ne gative MS patients (62% vs 55%), these were nor significantly different fro m controls. interactions were investigated between the Mva 1 alleles and T cell receptor beta chain variable region (TCRBV) germline polymorphisms, wi th a trend in MS individuals towards a decrease of the Mva 1*1 allele when combined with the TCRBV3S1*2 allele (Relative Risk=0.25, P=0.067), and with the TCRBV8S1*1 allele (Relative Risk=0.44, P=0.12). overall, the findings of this study indicate a possible effect of the APo-1/Fas promoter Mva 1 po lymorphism in MS susceptibility, which needs to be confirmed in further stu dies.