Risk factors of the development of multiple sclerosis in Moscow population: combination of exogenic and hereditary factors

Simultaneous study of both external and hereditary risk factors of the deve lopment of multiple sclerosis (MS) was carried out in Moscow population. As a result of the genotyping of HLA-DR locus on the chromosome 6, there were found markers of the predisposition to MS: by HLA-DR: DR2(15) way, especia lly, in homozygous heredity and in the absence of such specificity - allele s of DR3 group. The data were confirmed concerning both the elevation of fr equency of the alleles of tumor necrosis factor (TNF)a(1) and alpha(2) and the decrease of frequency of TNF-alpha(7) allele in MS. There was also conf irmed association of the disease with the external factors, such as "predom inance of the meat nutrition at the age under 15 years" and "tonsillitis at the age under 15 years". There were two combinations of the external and h ereditary factors, when the power of the association increased significantl y: "predominance of meat nutrition at the age under 15 years" and DR2(15) a nd "tonsillitis at the age under 15 years" and DR3. When genetic factors we re excluded, the relation of MS with the external factors was considerably reduced; when the external factors were excluded, the association of MS wit h genetic markers became statistically insignificant. A combination of thes e external factors, which were the sources for the additional antigenic imm unostimulation, with certain genetic factors in DR region suggested the pre sence of the genetically determinated peculiarities of the composition of a ntigen presentation HLA-DR in the individuals with DR2(15) and DR3. There w as no statistically confirmed presence of a combination of the external fac tors with TNF-alpha alleles which increased additionally MS risk. The prese nce of immunostimulating antigen-containing external factors may be signifi cant for the influence of TNF-alpha in less degree than for the realization of predisposition in form of the certain composition of HLA molecules.