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It is a well known fact that interleukin 6 (IL-6) stimulates the proliferation of neoplastic plasma cells and acts as an osteoclast-activating factor (plays an important role in the development of the bone disease), whereas interleukin 4 (IL-4) suppresses growth of multiple myeloma (MM) by inhibiting the synthesis of IL-6. Single nucleotide polymorphisms (SNPs) in the regulatory regions of cytokine genes may affect on the transcription and production of the cytokines that can effect on the development of various diseases.

The aim of this study was to identify SNP in different regions of IL-6 (-174G/C, nt565G/A) and IL-4 (-1098T/G, -590T/C, -33T/C) genes associated with the development of MM among the residents of the Northwest Federal District of Russia as well as determination of the bone lesions severity.

We analysed 43 MM patients with the median age 69 years. Patients were divided into two groups depending on the detected changes in the bones: 1^st group (19 patients) - with severe osteolytic bone lesions (III stage of the Durie-Salmon staging system); 2^nd group (24 patients) – with manifestations of osteoporosis and isolated pockets of osteolytic bone lesions (II stage of the Durie-Salmon staging system). The control group consisted of 40 healthy unrelated Caucasoid blood donors (median age 54 years). All analysed people were from the Northwest Federal District of Russia (St-Petersburg). Genomic DNA was extracted from the peripheral blood and both IL-4 and IL-6 gene genotyping was performed by the use of PCR-SSP.

Based on the genotyping results of IL-4 -1098T/G we found that in general cohort of patients with MM genotype frequencies were not significantly different from each other except for the IL-4 -1098GG genotype which was not detected in the group of healthy people but was registered in the group of patients with a frequency of 0.05. When we analysed data for IL-4 -590T/C the genotype frequency of IL-4 -590TC in patients was two times lower than in control group (0.25 vs. 0.53). Although genotype IL-4 -33TT in MM patients with manifestation of osteoporosis occurs three times often than in control group (0.33 vs. 0.10 respectively). Some differences in IL-6 -174GG genotype frequencies in patients with MM were observed: in a total group of patients - 0.47 (0.53 in the 1^st group and 0.42 in the 2^nd group) against 0.13 in the control group. ?onversely, the IL-6 -174GC genotype was more frequent in the group of donors than in the group of patients with severe osteolytic lesions (0.70 vs. 0.26 respectively). Similar pattern was observed for IL-6 nt565GA genotype - in control group this genotype was noticed more frequently (0.80) than in patients (from 0.26 in the 1^st group and 0.42 in the 2^nd group). However, IL-6 nt565GG genotype frequency was less common in healthy people compare to patients with MM (0.13 to 0.49 respectively). Finally, IL-6 nt565GG was significantly higher in patients with severe osteolytic bone lesions than in patients with symptoms of osteoporosis and in the control group (0.53 vs. 0.46 and 0.13 respectively).

Thus, our results allow to describe some genotypes as markers associated with the development of MM such as IL-4 -33TT, IL-6 -174GG and IL-6 nt565GG. Furthermore, IL-6 nt565GG genotype is associated with the development of severe osteolytic lesions in multiple myeloma.