Polymorphism of the cytokine genes IL-1β, TNF-α, IL-1Rа and preterm birth
Vera Belousova (RU), Alexander Strizhakov (RU), Oxana Svitich (RU), Irina Bogomazova (RU)
[Belousova] I.M. Sechenov First Moscow state medical university, [Strizhakov] I.M. Sechenov First Moscow state medical university, [Svitich] I.I. Mechnikov Scientific research institute of vaccines and sera, [Bogomazova] I.M. Sechenov First Moscow state medical university
Objective: The objective was to characterize polymorphism of the cytokine genes IL-1β, TNF-α and IL-1RA associated with term and spontaneous preterm birth. Patient(s): prospective study of gene polymorphism between the women who experienced spontaneous preterm birth (n=66) and who delivered at term (n=42). Methods: The polymorphic variants of these genes were determined by PCR. Result(s): The allele T of IL-1β + 3953C → T (rs1143634) cytokine gene was detected in 36.4% women with preterm birth and in 4.8% cases of term delivery respectively (p <0.05; RR = 1.802; 95% CI = 1.420-2.288). Genotype AA of TNF-α G → A (rs1800629) gene was not found. The genotype GA was identified 3.8 times more often in women with preterm birth (18.2% and 4.8%; p> 0.05; RR = 1.492; 95% CI = 1.133−1.966). Gene polymorphism of IL-1RA was identified 1.5 times more often in women with preterm birth (63.6% and 42.8%; p <0.05; RR = 1.400; 95% CI = 1.009−1.943). Genotype GA of TNF-α gene was always combined with the presence of IL-1β and IL-1RA pro-inflammatory cytokine genotypes and leads to the delivery in 24-26 weeks. The genotype TT of IL-1β gene was always combined with pro-inflammatory cytokine genotype of IL-1RA and lead to the delivery at 23-25 weeks. Genotype CT of IL-1β gene was combined with pro-inflammatory TNF-α and IL-1Ra genotypes in 66.7% of cases and all these women had early preterm birth. Conclusions. Detection of pro-inflammatory genotypes of the investigated cytokines can be attributed to those women at risk of preterm birth. The pro-inflammatory T allele of IL-1β +3954 cytokine gene and interleukin 1 receptor antagonist gene (IL-1RA) can be considered as a risk factor for preterm birth. The combination of pro-inflammatory genotypes is also a negative factor for the prolonging of pregnancy and was found only in women with early preterm birth.