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To study frequencies of occurrence of the combined genetic attributes including different variants of cytokines genotypes (TNFA, IL1B, IL4, IL6, IL10, VEGF), in different on sexual and age groups in population of Siberia Caucasoid.Frequencies of distribution of variants of structure genes cytokines networks among 500 representatives of Siberia Caucasian population, men and women of two age groups--more younger than 35 years ("young") and 55 and more years ("elderly") are investigated. In structure of investigated genes cytokines net has come 10 variants of polymorphic sites of cytokines genes and vascular endothelial growth factor gene: TNFA-863 C --A, TNFA-308 G --A, TNFA-238 G --A, IL1B-31 C --T, IL4-590 C --T, IL6-174 G --C, IL10-1082 G --A, IL10-592 A --C, VEGF-2578 C --A and VEGF+936 C --T. Genotyping are carried out by restriction fragment length polymorphism method. Processing of results carried out on the basis of the original methodological approach including the complex connected computer analysis of genic circuits of various dimension.It is shown, that the significant part of variants genes cytokines networks, which widely distributed among young people is completely absent in the "elderly" age group. Such variants disappearing with age separately for men and women are established. At the program mathematical analysis it is established, that parameters of the odds ratio achieve two-place sizes (OR = 27, p = 0,0004), that testifies to high specificity of complex genetic attributes. Presence in genome such variants of genes cytokines networks, found out in the childhood or young age, as supposed, is unfavorable personalized prognostic factors of life span of the individual.

To study the distribution of genotypes in the cytokine genes and their combinations with immunoregulatory activity in patients with type 2 diabetes mellitus (T2DM) and in healthy women.586 Europeoid women from the eastern regions of Russia, including 374 healthy women aged 23-68 years and 212 women aged 28-69 years with T2DM complicated and uncomplicated by osteoporosis, were examined. Seven polymorphisms located in the promoter regions of the interleukin (IL) gene: TNF-alpha at positions C-863A, G-308A, G-238A, IL1B T-31C, IL6 G-174C, IL10 C-592A, VEGFA C-2578A were investigated. Restriction analysis of amplification products was applied.There were high associations of the predisposition and resistance to the development of T2DM with a number of polylocus cytokine genotype combinations having pro- and anti-inflammatory, angiogenic, and immunoregulatory activities. The association of the cytokine genes with T2DM was found to be mediated in nature through a relationship of the genotypes to the high or low production of regulatory cytokines and to different factors of regulation of lipid and carbohydrate metabolisms, inflammation, and bone remodeling.The high odds ratio and high specificity of the detected genetic combinations allow one to hope that they will be clinically used as predictors.

Cytokines as regulators of activity of inflammation play significant role in mechanisms of formation of atherosclerotic plaques and in processes of their destabilization. One of leading genetic factors determining level of their production appears to be polymorphism of cytokine genes structure at their promoter loci. We have conducted an analysis of distribution in groups of healthy male and female survivors of myocardial infarction (MI) of combined genetic signs represented as a complex of genotypes of a number of studied cytokine genes : TNF-A863C; TNF-A308G; TNF-A238G; IL1B-C511T; IL1B-C-31T; IL4-C590T; IL6-C174G; IL10A-1082G IL10-A592C. Among these homozygous combinations of cytokine genotypes characterizing a group of men who have lived up to middle and old age without development of MI there are widely represented genotypes associated with high levels of production of both cytokines with pronounced proinflammatory (IL-1) and antiinflammatory (IL-4, IL-10) activity. Absence of such multidirectional combinations in genome of patients with myocardial infarction can be considered one of genetic factors of risk of development of acute distirbances of coronary circulation.

The article reports results of the first study of cytokine gene polymorphic sites and analysis of distribution of their complexes among healthy subjects and patients with rheumatoid arthritis (RA) representative of the Russian Europeoid population; their possible prognostic significance is evaluated. Comprehensive analysis of the frequency of allelic variants of cytokine genes IL1B C-31T, IL6 G-174C, TNFA A-238G, TNFA A-308G, TNFA A-863C, IL4 C-590T, IL10 A-592C and VEGF C-2578A was performed for 513 residents of the Novosibirsk region showing no obvious signs of any diseases and 125 RA patients. The results suggest association of RA with certain alleles of pro- and anti-inflammatory cytokine genes. Complex indices reflecting combinations of genotypes of two, three, four, five, six and seven loci of the explored cytokine genes found in individual patient demonstrate their high specificity for RA. It is supposed that these findings can be used in further clinical studies for the development of algorithm designed to detect risk groups among clinically healthy subjects.