A significant increased frequencies of the +3142 G allele and the 14 bp DEL / +3142 G haplotype were found in MS patients compared to HD. MS patients with the +3142 C/C genotype have lower age of disease onset (ADO). The +3142 C > G polymorphism may constitute a genetic susceptibility factor to MS in the Tunisian population. No association was found between the two polymorphisms and sHLA-G serum levels.