Bioinformatic analysis of the results of cytokine genotyping in a benign tumor process among Russian women of Caucasian origin

The aim of the work is the comparative analysis of the distribution of single nucleotide polymorphisms (SNPs) of regulatory regions of pro-inflammatory and anti-inflammatory cytokine genes among patients with uterine leiomyoma (UL) and healthy Russian women of Caucasian origin with assessment of the prognostic significance of the identified genetic differences. An observational genetic case-control study was carried out with the participation of 180 women aged 23–61 years with UL and 98 apparently healthy women of the same age (control group). Genotyping of SNPs of pro-inflammatory cytokine genes TNF-863C/A, TNF-308G/A, TNF-238G/A, ILIB-31T/C, IL6-174C/G, IL8-251T/A, ILI7-197A/G and anti-inflammatory cytokines IL4-590 CIT, ILI0-592 A/C, IL-I0-I082 A/G were performed using the RT-PCP method. Standard methods of genetic-statistical and bioinformatic analyzes were used. A comparative study of the frequency distribution of 10 SNPs of cytokine genes has identified 587 statistically significant, taking into account the Bonferroni correction, complex genotypes that were positively or negatively associated with the UL development. The strongest positive associations were represented by combinations of SNPs genes: TNF-308:ILI7-197: GG-AA (OR=7.03, p=0.0162), ILI0-I082:ILI7-197: AG-AA (OR=10.78, p=0.0423), TNF-308:IL6-174:ILI0-592:ILI0-1082:GG-GC-CC-AG (OR=12.81, p=O.0414). The predictive value of such biomarkers for susceptibility to UL ranges from 82 % to 100%. Also, a group of complex genotypes was identified, the frequency of which in patients with UL was significantly lower than in the control group (p<O.OI). Identification of such signs in a particular woman allows her to be classified as resistant to the UL development with a probability of 87% to 100%. The data obtained can be used to form a set of personalized prognostic indicators of a woman's genetic predisposition or resistance to the UL development even before the development of the benign tumor process.