RESUMO
OBJECTIVES: To determine whether histologic chorioamnionitis is associated with changes in gene expression of TLR-1, -2, -4 and -6, and to describe the localization of these receptors in fetal membranes. STUDY DESIGN: A total of 135 amniochorion membranes with or without histologic chorioamnionitis from preterm or term deliveries were included. Fragments of membranes were submitted to total RNA extraction. RNA was reverse transcribed and the quantification of TLRs expression measured by real time PCR. RESULTS: All amniochorion membranes expressed TLR-1 and TLR-4, whereas 99.1% of membranes expressed TLR-2 and 77.4% expressed TLR-6. TLR-1 and TLR-2 expressions were significantly higher in membranes with histologic chorioamnionitis as compared to membranes without chorioamnionitis in preterm pregnancies (p=0.003 and p<0.001, respectively). Among the membranes of term pregnancies there were no differences in the expressions of such receptors regardless of inflammatory status. Regarding TLR-4 and TLR-6 expression, there was no difference among membranes with or without histologic chorioamnionitis, regardless gestational age at delivery. TLR-1, TLR-2, TLR-4 and TLR-6 expressions were observed in amniotic epithelial, chorionic and decidual cells. CONCLUSION: Amniochorion membranes express TLR-1, TLR-2, TLR-4 and TLR-6 and increased expression of TLR-1 and TLR-2 is related to the presence of histologic chorioamnionitis in preterm pregnancies. This study provides further evidence that amniochorion membranes act as a mechanical barrier to microorganisms and as components of the innate immune system.
Assuntos
Corioamnionite/genética , Receptores Toll-Like/biossíntese , Adulto , Âmnio/metabolismo , Corioamnionite/metabolismo , Córion/metabolismo , Estudos Transversais , Membranas Extraembrionárias/metabolismo , Feminino , Expressão Gênica , Humanos , Trabalho de Parto Prematuro/metabolismo , Gravidez , Nascimento Prematuro/fisiopatologia , Receptor 1 Toll-Like/biossíntese , Receptor 2 Toll-Like/biossíntese , Receptor 4 Toll-Like/biossíntese , Receptor 6 Toll-Like/biossínteseRESUMO
OBJECTIVE: The purpose of this study was to determine whether maternal/fetal single nucleotide polymorphisms (SNPs) in candidate genes are associated with spontaneous preterm labor/delivery. STUDY DESIGN: A genetic association study was conducted in 223 mothers and 179 fetuses (preterm labor with intact membranes who delivered <37 weeks of gestation [preterm birth (PTB)]), and 599 mothers and 628 fetuses (normal pregnancy); 190 candidate genes and 775 SNPs were studied. Single locus/haplotype association analyses were performed; the false discovery rate was used to correct for multiple testing. RESULTS: The strongest single locus associations with PTB were interleukin-6 receptor 1 (fetus; P=.000148) and tissue inhibitor of metalloproteinase 2 (mother; P=.000197), which remained significant after correction for multiple comparisons. Global haplotype analysis indicated an association between a fetal DNA variant in insulin-like growth factor F2 and maternal alpha 3 type IV collagen isoform 1 (global, P=.004 and .007, respectively). CONCLUSION: An SNP involved in controlling fetal inflammation (interleukin-6 receptor 1) and DNA variants in maternal genes encoding for proteins involved in extracellular matrix metabolism approximately doubled the risk of PTB.
Assuntos
Estudos de Associação Genética , Trabalho de Parto Prematuro/genética , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-6/genética , Adulto , Estudos de Casos e Controles , Chile , Corioamnionite/genética , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Feminino , Ruptura Prematura de Membranas Fetais/genética , Predisposição Genética para Doença , Variação Genética , Haplótipos , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/fisiologia , Pré-Eclâmpsia/genética , Gravidez , Nascimento Prematuro/genética , Adulto JovemRESUMO
OBJECTIVES: To evaluate whether genotypes of interleukin (IL)-6 gene promoter positions -174 and -572 are associated with histologic chorioamnionitis and neonatal inflammatory disease in preterm infants. STUDY DESIGN: DNA from very low birth weight or very preterm infants (n = 107) was genotyped for IL-6-174 and -572 polymorphisms (GG/GC/CC). The placentas were analyzed for histological inflammatory findings. Data on neonatal inflammatory diseases, including chronic lung disease (CLD), necrotizing enterocolitis (NEC), and septicemia, were collected using the definitions of the Vermont Oxford Network database. RESULTS: In univariate analyses, the IL-6-174 GG genotype was associated with a higher incidence of histologic chorioamnionitis. In multivariate analyses, the -174 GG and -572 GC genotypes were correlated with histologic chorioamnionitis (P = .039 and .009, respectively). Gestational age was not associated with genotype polymorphisms. IL-6-174 genotypes were not associated with CLD and/or NEC, but the CC genotype was correlated with septicemia in both univariate and multivariate analyses (P = .027). IL-6-572 genotypes were not associated with neonatal inflammatory disease. CONCLUSIONS: The IL-6-174 GG and -572 GC genotypes were associated with a higher incidence of histologic chorioamnionitis, and the IL-6-174 CC genotype was associated with septicemia in preterm infants. These findings suggest that the genetic composition of the IL-6 promoter area plays a significant role in the pathogenesis of chorioamnionitis and neonatal infections.