Molecular genetic predictors of the efficiency of tocolytic therapy in pregnancy prolongation in threatened preterm labor

Objective. To study the pharmacogenetics of tocolytic therapy with a ß 2-adrenomimetic (hexoprenaline sulfate), by investigating cytokine and β-adrenergic receptor gene polymorphisms. Subject and methods. One hundred and three patients with threatened preterm labor who received tocolytic therapy with the selective ß 2-adrenomimetic hexoprenaline sulfate (gynipral) at 22-33 weeks’ gestation were examined. Polymerase chain reaction and a melting curve analysis were used to investigate 11 genes and 13 polymorphic gene loci. Results. The predictors of conception less than 7 days after acute tocolysis at 22-33 weeks’ gestation are the T/T genotype of the BSG 3800 gene (p=0.03, OR=5.18 (1.01-26.61) and IL10-592 A allele (р=0.05, OR=3.12 (0.88-11.06)). The T/T genotype of the IL1R1-15858C>T gene was associated with the possibility of prolonging a pregnancy > 34 weeks after acute tocolysis (OR=4.62 (1.17-18.20), p=0.02). The IL1RN: 390 C/C and VEGFA:936 С/С genotypes are predictors of conception less than 7 days after acute tocolysis at 22-27 weeks while after acute tocolysis at 28-33 weeks they exert no substantial impact on the possibility of prolonging a pregnancy > 34 weeks. Conclusion. There is a decrease in the role of infection in preterm labor in the third trimester of pregnancy and hence there is a reduction in the significance of genetic susceptibility to infectious agents. An infection-initiated tendency to activate an inflammatory cytokine cascade seems to be the main mechanism of the low efficiency of tocolytic therapy at 22-27 weeks in pregnancy prolongation, which is associated with the cytokine BSG 3800C>T, IL10.-592A>C, IL1R1-158580T, IL1RN: 390 C/C and VEGFA:936 С/Сgenes.

threatened preterm labor, tocolytic therapy, ß-adrenergic receptors, cytokine and ß-adrenergic receptor gene polymorphisms