The aim of the study was to develop technologies for predicting the development of preeclampsia (PE) based on biomedical and molecular-genetic predictors and the calculation of individual risks for this pregnancy complication.Materials and Methods. The study involved 457 pregnant women. Of them, 147 women had chronic arterial hypertension (CAH); 109 pregnant women had CAH and secondary preeclampsia (PE); 201 patients had PE. The control group consisted of 105 pregnant women without hypertensive disorders or proteinuria. We performed a retrospective analysis of gestation course and labor outcomes, calculated risk factors using the Open Epi system and logistic regression method. Polymorphisms of genes controlling the vascular tone were identified in venous blood.Results. There were identified risk factors for developing PE, including those in women with CAH: chronic pyelonephritis; baseline mean AP above 95 mm Hg and diastolic AP above 80 mm Hg; body mass index over 30; family history of arterial hypertension. The following were identified as additional predictors of PE: perinatal loss; premature labor; spontaneous miscarriage; PE and closed craniocerebral injuries in the past medical history; threatening miscarriage in the first trimester. Additional risk factors for PE in women with CAH were found: lack of regular antihypertensive therapy before pregnancy and in the first trimester; chronic gastritis; first pregnancy; tobacco smoking.Polymorphic variants of the NOS3 (-786)C allele in the genotype in combination with the heterozygous genotype in the AGTR2 1675G/A gene are associated with a high risk of CAH. The presence of alleles NOS3 (-786)T/C and NOS3 (-786)C, as well as a combination of alleles NOS3 (-786)C and NOS3 894G/T, is associated with PE. The presence of alleles AGT 704C, CYP11B2 (-344)T, and GNB3 825T/T in the genotype, both individually and in combination, is a risk factor for the development of PE secondary to CAH. The data obtained made it possible to develop a method for predicting the onset of PE in women with CAH and a model for calculating the individual risk of PE, which formed the basis for a computer program. Conclusion.Calculating the individual risks of PE using the technologies proposed by the authors allows identifying pregnant women belonging to the high-risk group on a timely basis, which ensures high-quality implementation of preventive measures, provides a personalized approach and the possibility to prove the need for additional examination of this category of patients.

Цель исследования. Изучение особенностей полиморфизма генов системы HLA II класса (DRB1, DQA1, DQB1) у глубоконедоношенных новорожденных с массой тела при рождении менее 1500 г, имеющих врожденную пневмонию, и определение факторов риска формирования данного заболевания. Материал и методы. Проведено комплексное обследование 103 новорожденных: в 1-ю группу вошли дети с клинико-лабораторными признаками врожденной пневмонии (n=61), во 2-ю-дети с респираторным дисстрес-синдромом и без врожденной пневмонии (n=42). Геномную ДНК выделяли из лимфоцитов венозной крови и эпителиальных клеток буккального соскоба, тестирование генов HLA II класса проводили с использованием классической полимеразной цепной реакции. Результаты. В группе детей с врожденной пневмонией выявлено увеличение частоты аллелей DRB1*04 и DRB1*15, а также генотипа DQB1 0302/0602, что может свидетельствовать о предрасполагающем к развитию данного заболевания эффекте указанных генов и служить молекулярно-генетическим предиктором формирования данного заболевания. В генотипе у недоношенных новорожденных с врожденной пневмонией достоверно реже встречались аллели DRB1*13, DQA1*0103, DQB1*0501, DRB1*13/13; DQA1*0101/0103; DQB1*0501/0602; GSTM1 +/+ GSTТ1 +/+ DRB1*13 DQA1*0501 DQB1*0301, оказывающие протективный эффект в отношении развития воспаления в легочной ткани. Статистически значимых различий по частоте низкофункциональных аллелей генов семейства глутатитон-S-трансфераз (GSTM1 и GSTT1) в ходе настоящего исследования не обнаружено. Заключение. Результаты проведенного исследования могут быть использованы для персонификации лечебно-диагностического процесса и выхаживания глубоконедоношенных новорожденных. Ключевые слова: глубоконедоношенные новорожденные, врожденная пневмония, факторы риска, генетические факторы, полиморфизм генов, гены детоксикации, главный комплекс гистосовместимости.

The features of polymorphism of genes characterizing the functional state of the vascular wall in newborns born to mothers with preeclampsia were studied. 150 children were examined, the main group consisted of 100 newborns born to mothers with preeclampsia (PE), the control group included 50 children born to women without preeclampsia. Single-nucleotide polymorphisms were determined in the blood of newborns: ADD1 G1378T (rs4961), AGT T704C (rs699), AGT C521T (rs4762), AGTR1 A1166C (rs5186), AGTR2 G1675A (rs1403543), CYP11B2 –344 C/T (rs1799998), GNB3 C825T (rs5443), NOS3 –786 T/C (rs2070744), NOS3 G894T (rs1799983) using the real-time polymerase chain reaction method with the DTprime 5 device (DNA-Technology, Russia) and the Cardiogenetics kit (DNA-Technology, Russia). The genetic analysis revealed that newborns born to mothers with PE were significantly more likely to have unfavorable genotypes АDD1 1378 G/T, AGT 704 T/C, AGT 704 C/C, AGTR2 1675 A/A, NOS3 (-786) C/C, NOS3 894T/T and alleles АDD1 1378T, AGT 704 C, AGTR2 1675A, NOS3 (-786) C, NOS3 894T. In newborns from mothers without PE, genotypes homozygous for the “wild type” alleles were significantly more common: АDD1 1378 G/G, AGT 704 T/T, CYP11B2 (-344) C/C, NOS3 (-786) T/T, NOS3 894 G/G and the NOS3 (-786) T allele. The revealed changes in newborns born to mothers with PE indicate an increased risk of developing disorders of the cardiovascular system.

The aim of the research was to study the polymorphism of the genes of the detoxification system and genes of the main histocompatibility complex HLA class II in premature infants with a birth weight of less than 1500 g and a gestation period of less than 32 weeks. Materials and methods of research: 103 extremely premature infants without congenital malformations, having respiratory disorders and requiring respiratory therapy in one volume or another, were under observation. All children were divided into 2 groups: 1st – 81 extremely premature babies with favorable outcome (recovery); 2nd – 22 children with unfavorable outcome (death, disability). Results: an association was established between the presence of DQA1*0301 alleles in the genotype and the development of unfavorable outcome in extremely premature infants with respiratory pathology (p=0.041). In addition, the genotype GSTM1+/+ GSTT1+/+ DRB1*13 DQA1*0301 DQB1*0602 was determined only in children with poor outcomes (p=0.041). The presence of genotypes GSTM1 – GSTT1+/+ DRB1*11 DQA1*0501 DQB1*0301 and GSTM1 – GSTT1+/+ DRB1*15 DQA1*0102 DQB1*0602 17 times, and the presence of the DQA1*0401 allele 8 times increases the risk of death (p=0.028).