Issue: 2026, Vol. 31, No. 1

M. P. Grishchuk (Dmitrieva), E. A. Leonova, I. V. Orlov, E. A. Grechikha

EFFECT OF IL-18:-137G>C GENE POLYMORPHISM ON LOCAL RESCUE RESPONSE AND RISK OF COMPLICATED PREGNANCY IN I-II TRIMESTERS

Keywords

IL-18:-137G>C gene polymorphism, pregnancy, cytokines, vaginal microbiocenosis, pregnancy complications, premature birth

Abstarct

The aim of this study is to evaluate the impact of IL-18:-137G>C gene polymorphism on the local inflammatory response, specifically tumor necrosis factor-alpha (TNFα), interleukins (IL-8, IL-1, IL-2, IL-6, IL-10, and IL-18), vaginal microbiocenosis, and the incidence of complications during early pregnancy. Material and Methods. The interim results of a prospective cohort study including 125 pregnant women at 11-13 weeks and 6 days of gestation are presented. At 11-13 weeks, the genotype of the IL-18:-137G>C polymorphism was determined using the polymerase chain reaction (PCR). At 16-17 weeks, cytokine concentrations (TNFα, IL8, IL18, IL-1, IL-6, and IL-10) were assessed in the lower reproductive tract using enzyme immunoassay (ELISA). The composition of the vaginal flora was also assessed using real-time PCR (Femoflor-16, Russia). Statistical analysis was performed using non-parametric tests with the Benjamini- Hochberg correction for multiple comparisons (FDR <0.05). Results and Discussion. The CC genotype was associated with a hyperinflammatory phenotype. In firsttime pregnancy, carriers of the CC genotype showed significantly higher levels of TNF-α, IL-6, and IL-18 (5.3-, 28-, and 3.5-fold, respectively; p < 0.01), as well as a lower level of IL-10 (p < 0.01) compared to GG carriers. In repeat pregnancies with the CC genotype, only IL-10 levels significantly decreased (p < 0.01). First-time pregnancies with CC showed a sharp increase in opportunistic pathogens, such as Gardnerella/ Prevotella/Porphyromonas (by 100-fold), Sneathia/Leptotrichia/Fusobacterium (by 1,000-fold) and Atopobium vaginae (by 10-fold; p < 0.01; FDR < 0.05). Carriers of the CC genotype were at the highest risk for complications in the first and second trimesters of pregnancy, including the threat of pregnancy termination (53.8% in first-time pregnancies; p = 0.009), anemia (61.5%; p = 0.003), and bacterial vaginosis (36.4%; p = 0.002) in repeat pregnancies. Conclusion. Polymorphism of the IL-18: -137G>C gene is a significant predictor of microbiocenosis disorders and obstetric complications during the I-II trimesters of pregnancy. The most unfavorable profile is associated with the CC genotype especially in first-time pregnant women. Identification of this polymorphism at an early stage of gestation may help identify high-risk groups and implement personalized approaches to preventing complications.

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• Quid est Veritas_1_ 2026-47-54