Distribution of variants of the TNFA gene regulatory sites among Russian women of Caucasian origin with leiomyoma

The importance of cytokines, including TNF, in development of uterine fibroids (UF) or leiomyomas (LM) is well proven. The number of polymorphic sites in promoter region of TNF gene is established, and their relationship with the gene expression level has been shown, thus potentially affecting the evolution of the disease. The aim of our research was to analyze the distribution of TNF -238, TNF - 308 and TNF -863 structural variants at the regulatory region of the TNFA gene in a representative group of Caucasian patients with UF compared with a matched group of healthy women followed by assessment of personalized prognostic significance of suggested differences. 180 patients diagnosed with uterine fibroids and 98 practically healthy women were examined. Genotyping of TNF gene polymorphisms ( -863 C/A, TNF- 308 G/A, TNF-238 G/A, IL1B-31 T/C, IL4-590 T/C, IL6-174 C/G, IL8-251 T/A, IL10-592 A/G, IL10-1082 A/G and IL17A-197 G/A ) was performed by RT-PCR using the SYBR Green intercalating dye. Statistical processing was carried out using multifunctional programs – IBM SPSS Statistics 23, SNPStats. We did not reveal significant differences between the compared groups when analysing distribution of TNF allelic variants and their combinations in genotypes. When comparing the combined SNP variants of the TNF gene at the studied nucleotide positions with the polymorphisms of other genes encoding proinflammatory cytokines, an increased frequency of TNF-238 GG:TNF-308 GG:IL17A-197 AA complex was found in the group of patients with uterine fibroids. The diagnostic specificity of this index was 100%, and the predictive value of this quotient reached 13.3, thus implying a 99.9% probability of a correct prediction. At the same time, the combination of TNF-863 CC genotype with IL-6-174 GG and IL-17-197 GG was significantly reduced in the patients. The frequencies of the anti-inflammatory cytokine genes IL4-590 T/C, IL10-592 A/G and IL10-1082 A/G analyzed n our study did not differ in the both compared groups and they were not considered either predisposing or protective for the disease. The magnitude of the revealed differences in occurrence of these allelic combinations reaches a significant level, thus assuming these traits as potential genetic factors for predicting a predisposal or resistance of women with a certain genotype to development of uterine fibroids, being prognostic criteria for early detection of this disorder.