[The risk factors for the development of multiple sclerosis in the Moscow population. II. The combination of exogenous and hereditary factors].
Simultaneous study of both external and hereditary risk factors of the development 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, especially, in homozygous heredity and in the absence of such specificity--alleles of DR3 group. The data were confirmed concerning both the elevation of frequency of the alleles of tumor necrosis factor (TNF)a1 and alpha 2 and the decrease of frequency of TNF-alpha 7 allele in MS. There was also confirmed association of the disease with the external factors, such as "predominance 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 hereditary factors, when the power of the association increased significantly: "predominance of meat nutrition at the age under 15 years" and DR2(15) and "tonsillitis at the age under 15 years" and DR3. When genetic factors were excluded, the relation of MS with the external factors was considerably reduced; when the external factors were excluded, the association of MS with genetic markers became statistically insignificant. A combination of these external factors, which were the sources for the additional antigenic immunostimulation, with certain genetic factors in DR region suggested the presence of the genetically determined peculiarities of the composition of antigen presentation HLA-DR in the individuals with DR2(15) and DR3. There was no statistically confirmed presence of a combination of the external factors with TNF-alpha alleles which increased additionally MS risk. The presence of immunostimulating antigen-containing external factors may be significant for the influence of TNF-alpha in less degree than for the realization of predisposition in form of the certain composition of HLA molecules.
Gusev
E I
EI
Boĭko
A N
AN
Demina
T L
TL
Sudomoina
M A
MA
Alekseev
A P
AP
Boldyreva
M N
MN
Trofimov
D Iu
DIu
Favorova
O O
OO
D000293:Adolescent; D000483:Alleles; D002648:Child; D004247:DNA / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006684:HLA-DR Antigens / Q000235:genetics; D006801:Humans; D017720:Molecular Epidemiology; D009031:Moscow / Q000453:epidemiology; D009103:Multiple Sclerosis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics; D012307:Risk Factors; D014069:Tonsillitis / Q000453:epidemiology / Q000235:genetics; D014505:Urban Population / Q000706:statistics & numerical data*
D005819:Genetic Markers; D006684:HLA-DR Antigens; D004247:DNA
Faktory riska razvitiia rasseiannogo skleroza v moskovskoĭ populiatsii. II. Sochetaniia ékzogennykh i nasledstvennykh faktorov.