Fetal polymorphisms in anti-inflammatory cytokine and β-adrenergic receptor genes associated with placental pathological lesions

Prematurity is the leading cause of infant morbidity and mortality. Altered intra-amniotic levels of anti-inflammatory cytokines, interleukin (IL) 1ra and IL-4, and β2-adrenergic receptor (β2AR) production have been associated with preterm labor and delivery. The aim of this study was to evaluate potential associations of polymorphisms in these genes with specific placental pathological findings. Maternal and fetal DNA were analyzed for a length polymorphism in the IL-1ra gene and for single nucleotide polymorphisms in the IL-4 and β2AR genes. Placentas were evaluated for pathological abnormalities in the following major categories: meconium, malperfusion, acute deciduitis, chorioamnionitis, umbilical cord problems, villitis, and fetal vascular thrombosis. In fetal DNA, homozygosity for the IL-1ra 2 allele (P = 0.029) and carriage of the IL-4 T allele (P < 0.01) were associated with acute deciduitis. In addition, carriage of the β2AR A allele (P = 0.036) was associated with umbilical cord problems. There were no associations between placental lesions and any maternal gene polymorphisms. Although susceptibility to premature delivery is multifactorial, the present study provides pathological evidence for a connection between specific alleles and placental abnormalities. Carriage of these alleles may render the fetus more susceptible to the adverse consequences of infection and inflammation.