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Aim. Investigation of the association between SNP genes of IL4 (rs2243250), IL10 (rs1800896 and rs1800872) and RLN2 (rs4742076 and rs3758239) and preterm premature rupture of membranes in 26-34 weeks of gestation in Zaporizhzhia population. Materials and methods. We have investigated markers of cytokines genes in 50 women with PPROM in 26-34 weeks of gestation period and 50 pregnant women with physiological pregnancy and term labour without complications. The genotyping using TaqMan tests was done on amplifier CFX96™ Real-Time PCR Detection Systems (Bio-Rad Laboratories, Inc., USA. The combined effect of the studied locus of the analyzed genes on the appearance of PPROM, PTL in the population was initiated using the Multifactory Dimensionality Reduction (MDR) method (software MDR ver. 3.0.2). Results. The distribution of the rs2243250 gene polymorphism alleles of the IL4 gene of the main study group-TT homozygotes were determined in 4 % cases, CT heterozygotes were found in 22 %, CC homozygotes-in 74 % cases. We have got statistically significant differences of rs4742076 polymorphisms (TT, CT, and CC) of the RLN2 gene in the study groups. We also detected statistically significant differences in all the alleles of rs3758239 polymorphism (AA, GG and AG) of the gene RLN2-χ 2 = 23.86, OR(AA) = 12.57; 95 % CI: 3.68-42.98; OR(GG)= 0.08; 95 % CI: 0.02-0.27; and OR(AG)= 0.11; 95 % CI: 0.03-0.42, respectively, P < 0.05, indicating the reliability of the received prognostic markers. The nature of interlocal interaction between the genes is at the level of "independent effects" of influence (IL4-IL10 rs1800896 =-23.08 %, IL10 rs1800896-IL10 rs1800872 =-19.94 %, IL10 rs1800872-IL-4 =-19.34 %). The percentage of entropy of the investigated polymorphism of each gene for the case-control status was 14.15 % for the IL4 gene, 23.08 % for the IL10 rs1800896 gene and 9.34 % for the IL10 rs1800872 gene. Conclusions. Combination of IL4 rs2243250, IL10 rs1800896 and rs1800872 supports the role for functional polymorphisms in immunoregulatory genes in the development of PPROM and PTL. Reliable clinical association of rs4742076 and rs3758239 gene RLN2 was established with the PPROM in 26-34 weeks' gestation in Zaporizhzhia population.

The role of angiogenesis factors and hormonal profile in pregnant women with arterial hypertension has not been detailed studied, and their interaction in such patients has not been determined at present time.The objective: to determine the features of angiogenesis factors and hormonal profile in pregnant women with arterial hypertension of the 1and 2 grade. Materials and methods. A prospective study was conducted in 88 pregnant women, which included: analysis of clinical and anamnestic characteristics and the study of pregnancy characteristics in women with chronic arterial hypertension (CAH) in the I trimester of pregnancy (11–12 weeks). The open prospective controlled study involved 61 pregnant women with CAH of the 1 and 2 stages which consisted the main group. The control group included 27 healthy pregnant women with physiological pregnancy. Concentrations of human chorionic gonadotropin (hCG), progesterone (PG), estradiol (E) and markers of angiogenesis – placental growth factor (PlGF) as a proangiogenic factor and soluble fms-like tyrosine kinase (sFlt-1) as an antiangiogenic factor were determined in the blood serum of all patients, sFlt-1/PGF ratio was also estimated (K). Statistical analysis was performed using «STATISTICA® for Windows 13.0».Results. In the I trimester of pregnancy in women with CAH, a shift in the balance between pro- and anti-angiogenic factors is determined, which is manifested by a statistically significant (p<0.05) increase sFlt-1 level (1700.9 pg/ml) and a decrease PlGF level in 3.7 times (9.1 pg/ml) and, accordingly, an increase K coefficient (sFlt-1/PlGF) by 5.3 times (184.5). The mean concentrations of E, PG and hCG in pregnant women of the main group did not differ statistically significantly from those in the control group. However, according to the results of the correlation analysis, PlGF and PG indicators have feedback in pregnant women with CAH (r=-0.29; p<0.05). When calculating the correlation of PlGF and hormones, it was found that in pregnant women with CAH there is their growth according to the control group, namely the indicator hCG correlates with PlGF (51.8 units vs. 14.8 units) 3.5 times, E correlates with PlGF (309.7 units vs. 70.0 units) 4.4 times and PG correlates with PlGF (4.8 units vs. 1.0 units) 4.8 times (p<0.001 for all indicators). These changes indicate the presence of angiogenesis disorders in pregnant women with chronic hypertension, starting from the I trimester of gestation.Conclusions. Pregnant women with CAH in the I trimester have disturbances in balance between pro-angiogenic and anti-angiogenic factors with prevalence of sFlt-1 and decrease of PlGF in blood serum. Because of such imbalance in pregnant women with CAH of the 1 and 2 grade, the interaction of angiogenesis factors and hormones changed from direct to inverse. It may lead to the development of placental dysfunction in the future, so treatment and prevention should be provided for the pregnant women with CAH in the I trimester.

The role of the factors of angiogenesis and hormones of pregnancy in pregnant women with hypertension has been studied inadequately and their interaction in such patients is not fully elucidated at present time. Aim. To detect peculiarities of angiogenesis factors and placental hormones in pregnant women with arterial hypertension I and II grades in comparison with results of healthy pregnant women. Materials and methods. Conducting a prospective study of 88 pregnant women, which included: analysis of clinical and anamnestic characteristics and study of the peculiarities of pregnancy in women with chronic hypertension in the first trimester of pregnancy (11-12 weeks). The open prospective controlled study involved 61 pregnant women with chronic arterial hypertension (CAH) 1-2 degree, who were included in the first - the main group. The second control group included 27 healthy pregnant women with physiological pregnancies. Among the angiogenesis indices, the placental growth factor (PlGF), as a pro-angiogenic factor and placental soluble fms-like tyrosine kinase (sFlt-1) was determined as an anti-angiogenic factor, sFlt-1/PlGF ratio was also estimated. Statistical analysis was done by using «STATISTICA® for Windows 6.0» (Stat Soft Inc., № AXXR712D833214FAN5). Results. In the first trimester of pregnancy (11-12 weeks of gestation) in women with CAH is determined by a shift in the balance between pro- and antiangiogenic factors, manifested by statistically significant (p˂0.05) increase in sFlt-1 levels (1700, 9 pg / ml) and a decrease in PlGF levels in3.7 times (9.1 pg / ml) and, accordingly, an increase in the levels of the coefficient K in 5.3 times (sFlt-1 / PlGF) (184.5). The mean values of estradiol, progesterone and chorionic gonadotropin levels in pregnant women with CAH did not differ statistically significantly from those of the control group (p˃0.05). These changes indicate the presence of angiogenesis disorders in pregnant women with chronic hypertension, starting from the first trimester of gestation. Conclusions. Pregnant women with CAH in І trimester have disturbances in balance between pro-angiogenic and anti-angiogenic factors with prevalence of sFlt-1 and reducing of PlGF in serum plasma. Due to such disbalance in pregnant women with CAH of 1 and 2 grade changed cooperation between angiogenesis factors and hormones from direct to inverse. It may lead to development of placental insufficiency in future. That’s why treatment/prophylaxis of it should be administered to pregnant women with CAH in 1 trimester.

The objective: to assess and establish the relationships between Doppler blood flow indicators in the uterine arteries, angiogenesis factors and hormones of the mother-placenta-fetus system in pregnant women with arterial hypertension I-II degree.Materials and methods. A prospective study of 88 pregnant women at 11–12 weeks of gestation was carried out: 61 pregnant women with chronic arterial hypertension (CH) of the I–II degree (main group) and 27 healthy pregnant women with physiological pregnancy (control group). All patients have been examined: blood flow Doppler in the left and right uterine arteries – pulsation index (PI), resistance index (IR) and systolic-diastolic ratio (SDR). Chorionic gonadotropin (HCG), progesterone (PG), estradiol (E) and angiogenesis indices (placental growth factor (PlGF) as a pro-angiogenic factor) and placental-soluble fms-like tyrosine kinase (sFlt-1) as an anti-angiogenic factor and the ratio of sFlt-1/PlGF) were determined in blood. Statistical analysis was performed using the program “STATISTICA 13”.Results. There was no statistically significant difference in SDR and IP indicators between the groups. PI values in the right uterine artery in pregnant women of the main group were significantly higher than the indicator of healthy pregnant women (1.73 (1.65; 1.8) units versus 1.33 (1.1; 1.49) units, respectively). The PI values in the left uterine artery in pregnant women with CAH also significantly differed from those in women with the physiological course of pregnancy (1.7 (1.66; 1.79) units and 1.35 (1.22; 1.51) units, respectively). A significant correlation between SDR indicators and markers of angiogenesis and hormonal profile in women of the main group has not been established. In pregnant women with CAH, an inverse relationship was observed between PI and PlGF (mean strength R=-0.34 for PI in the right uterine artery and R= -0.41 for PI in the left uterine artery), respectively, between PI and sFlt-1/PlGF – direct relationship (average strength R=+ 0.37 for PI in the right uterine artery and R=+0.43 for PI in the left uterine artery). In women with the physiological course of pregnancy and childbirth, the PI value in the right uterine artery correlated with the sFlt-1/PlGF ratio (direct relationship) and PlGF level (feedback). PI in the left uterine artery had a direct relationship with the value of the sFlt-1/PlGF ratio. In pregnant women with CAH, the PlGF level decreases, while the PI value, on the contrary, increases.Conclusions. The significant differences between the indicators of SDS and IR in pregnant women with CAH and pregnant women without CAH have not been established. In women with CAH, significantly higher PI values were found in the right and left uterine arteries compared to those in women without CAH. The course of pregnancy in women with CAH is accompanied by a shift in the balance between pro- and anti-angiogenic factors, as evidenced by a statistically significant increase in sFlt-1 level against the background of a decrease in PlGF level, as well as a corresponding increase in the sFlt-1/PlGF ratio as compared with pregnant women without CAH. There are no correlations between indicators of SDR and IR in the uterine arteries, markers of angiogenesis and hormonal profile in pregnant women with and without CAH. Nevertheless, PI values in the right and left uterine arteries correlate with the PlGF level (feedback) and the sFlt-1/PlGF ratio (direct relationship) in pregnant women with CAH. This indicates the presence of disorders in this contingent of women in the I trimester of pregnancy.