Dataset Information

Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes.

ABSTRACT:

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.

SUBMITTER: Romero R

PROVIDER: S-EPMC3604889 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Publications

Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes.

Romero Roberto R Velez Edwards Digna R DR Kusanovic Juan Pedro JP Hassan Sonia S SS Mazaki-Tovi Shali S Vaisbuch Edi E Kim Chong Jai CJ Chaiworapongsa Tinnakorn T Pearce Brad D BD Friel Lara A LA Bartlett Jacquelaine J Anant Madan Kumar MK Salisbury Benjamin A BA Vovis Gerald F GF Lee Min Seob MS Gomez Ricardo R Behnke Ernesto E Oyarzun Enrique E Tromp Gerard G Williams Scott M SM Menon Ramkumar R

American journal of obstetrics and gynecology 20100501 5

<h4>Objective</h4>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.<h4>Study design</h4>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 ...[more]

PMID: 20452482

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Project description:BackgroundIntrauterine infection may play a role in preterm delivery due to spontaneous preterm labor (PTL) and preterm prolonged rupture of membranes (PPROM). Because bacteria previously associated with preterm delivery are often difficult to culture, a molecular biology approach was used to identify bacterial DNA in placenta and fetal membranes.Methodology/principal findingsWe used broad-range 16S rDNA PCR and species-specific, real-time assays to amplify bacterial DNA from fetal membranes and placenta. 74 women were recruited to the following groups: PPROM <32 weeks (n = 26; 11 caesarean); PTL with intact membranes <32 weeks (n = 19; all vaginal birth); indicated preterm delivery <32 weeks (n = 8; all caesarean); term (n = 21; 11 caesarean). 50% (5/10) of term vaginal deliveries were positive for bacterial DNA. However, little spread was observed through tissues and species diversity was restricted. Minimal bacteria were detected in term elective section or indicated preterm deliveries. Bacterial prevalence was significantly increased in samples from PTL with intact membranes [89% (17/19) versus 50% (5/10) in term vaginal delivery p = 0.03] and PPROM (CS) [55% (6/11) versus 0% (0/11) in term elective CS, p = 0.01]. In addition, bacterial spread and diversity was greater in the preterm groups with 68% (13/19) PTL group having 3 or more positive samples and over 60% (12/19) showing two or more bacterial species (versus 20% (2/10) in term vaginal deliveries). Blood monocytes from women with PTL with intact membranes and PPROM who were 16S bacterial positive showed greater level of immune paresis (p = 0.03). A positive PCR result was associated with histological chorioamnionitis in preterm deliveries.Conclusion/significanceBacteria are found in both preterm and term fetal membranes. A greater spread and diversity of bacterial species were found in tissues of women who had very preterm births. It is unclear to what extent the greater bacterial prevalence observed in all vaginal delivery groups reflects bacterial contamination or colonization of membranes during labor. Bacteria positive preterm tissues are associated with histological chorioamnionitis and a pronounced maternal immune paresis.

Project description:Successful pregnancy requires a tightly-regulated equilibrium of immune cell interactions at the maternal-fetal interface (i.e., the decidual tissues), which plays a central role in the inflammatory process of labor. Most of the innate immune cells in this compartment have been well characterized; however, adaptive immune cells are still under investigation. Herein, we performed immunophenotyping of the decidua basalis and decidua parietalis to determine whether exhausted and senescent T cells are present at the maternal-fetal interface and whether the presence of pathological (i.e., preterm) or physiological (i.e., term) labor and/or placental inflammation alter such adaptive immune cells. In addition, decidual exhausted T cells were sorted to test their functional status. We found that (1) exhausted and senescent T cells were present at the maternal-fetal interface and predominantly expressed an effector memory phenotype, (2) exhausted CD4+ T cells increased in the decidua parietalis as gestational age progressed, (3) exhausted CD4+ and CD8+ T cells decreased in the decidua basalis of women who underwent labor at term compared to those without labor, (4) exhausted CD4+ T cells declined with the presence of placental inflammation in the decidua basalis of women with preterm labor, (5) exhausted CD8+ T cells decreased with the presence of placental inflammation in the decidua basalis of women who underwent labor at term, (6) both senescent CD4+ and CD8+ T cells declined with the presence of placental inflammation in the decidua basalis of women who underwent preterm labor, and (7) decidual exhausted T cells produced IFNγ and TNFα upon in vitro stimulation. Collectively, these findings indicate that exhausted and senescent T cells are present at the human maternal-fetal interface and undergo alterations in a subset of women either with labor at term or preterm labor and placental inflammation. Importantly, decidual T cell function can be restored upon stimulation.

Dataset Information

Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes.

Objective

Study design

Results

Conclusion

Publications

Identification of fetal and maternal single nucleotide polymorphisms in candidate genes that predispose to spontaneous preterm labor with intact membranes.

Similar Datasets

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