Эндотелиальная дисфункция при привычном невынашивании беременности: генетические факторы и факторы внешней среды

Abstract

Objective. To examine the association between the carriage of endothelial dysfunction-related gene polymorphisms and recurrent pregnancy loss (RPL). Patients and methods. This case-control study included 87 patients who were divided into two groups. The study group consisted of 65 patients with a history of two or more consecutive pregnancy losses (2 to 11 losses). Primary RPL was detected in 20 patients, secondary in 26, and tertiary in 19. The control group consisted of 22 women with a history of three or more full-term births without episodes of miscarriage. The frequency of polymorphisms of the VEGFA -634G>C and IL6 -174G>C genes was determined by a ready-to-use real-time polymerase chain reaction (RT-PCR) test kits. Results. Carrying the VEGFA -634G>C GC genotype increases the risk of RPL 4-fold (p = 0.0072) and the IL6 -174G>C GC genotype – 3-fold (p = 0.028). Analysis of the impact of combinations of unfavorable genotypes showed that 65.0% of patients with primary RPL, 61.5% with secondary RPL, 63.2% with tertiary RPL, and 9% of healthy controls had a combination of GC VEGFA -634G>C and CC IL6 -174G>C. One of the key environmental factors determining the realization of susceptibility genes is age: the maximum age at the time of the first intended pregnancy was observed in patients with primary RPL (32.6 years vs. 25.5 years in the control group; p < 0.05), with 9% of healthy controls having a combination of two genotypes associated with pregnancy loss. That is, successful pregnancy at a younger age is possible even when carrying multiple risk alleles. The birth interval length is also important for successful pregnancy: a short inter-pregnancy interval allows to carry out the reproductive function during the most favorable period of the reproductive system before the influence of genotypes predisposing to RPL begins. Other environmental factors leading to the realization of carriage of RPL risk alleles include a history of intrauterine interventions and sexually transmitted infections. Conclusion. Study of the VEGFA -634G>C and IL6 -174G>C gene polymorphisms may serve as an effective method to predict RPL. For patients carrying these unfavorable gene polymorphisms, it is especially important to perform the reproductive function in time, i.e., before the realization of environmental factors. Key words: recurrent pregnancy loss, VEGF, endothelial dysfunction, susceptibility genes