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The article contains results concerning combination frequency analysis for a wide number of three- to six-locus constellations of cytokine gene alleles, i.e., IL-1B T-31C, IL-6 G-174C, TNFA G-238A, TNFA G-308A, TNFA C-863A, IL-4 C-590T, IL-10 C-592A. The study was performed in a group of 104 patients with rheumatoid arthritis (RA) who were subject to basic therapy with methotrexate. An association was found between certain individual multi-locus allele combinations, and efficiency of the therapy, as defined by decrease in DAS28 index following 24 week of methotrexate treatment. An association was demonstrated between adverse effects of drugs used, and a "cytokine genotype" of the patients. Analysis of the results was carried out with respect to correlations between the levels of pro- and anti-inflammatory cytokine production and promoter polymorphisms of respective genes. We assume that further clinical research will allow to use our results as pharmacogenetic criteria in order to choose more effective personalized therapies, taking into account the genotypes of RA patients.

Abstract. The article includes results of studying frequency distributions of polymorphic genotypes forsome genes regulating angiogenesis, i.e., MMP and VEGF, and their combinations with genotypes of some cytokines showing pro-angiogenic activity in patients with diabetes mellitus type 2 (DM2) and healthy controls. Angiogenesis-inducing MMP2-MMP9-VEGF genotype constellations have been shown to be more common in DM patients, thus presumably causing an imbalance between activation and suppression signals, being connected with C alleles of VEGF and MMP2, as well as with harboring of MMP9 C allele. Certain genotypes of IL-1B, IL-4, IL-10, IL-6, and TNFA, along with MMP and VEGF variants are more common within combined genetic patterns in DM patients. It is suggested that allelic combination studies of angiogenesis- and inflammation-regulating genes are necessary for understanding the DM2 pathogenesis, taking into account genetic control mechanisms influencing basic production levels of these regulatory factors.