Ethnic Differences in Key Candidate Genes for Spontaneous Preterm Birth: TNF-α and Its Receptors

2006 ◽  
Vol 62 (2) ◽  
pp. 107-118 ◽  
Author(s):  
Ramkumar Menon ◽  
Digna R. Velez ◽  
Poul Thorsen ◽  
Ida Vogel ◽  
Bo Jacobsson ◽  
...  
2017 ◽  
Author(s):  
Sara R van Boeckel ◽  
Heather MacPherson ◽  
Donald J Davidson ◽  
Jane E Norman ◽  
Sarah J Stock

AbstractPreterm birth is the leading cause of neonatal mortality. While spontaneous preterm birth (sPTB) is the cause of over 70% of PTB, the pathogenesis behind sPTB remains unclear. Cell-free fetal DNA (cff-DNA) originates from the placenta and is increased in women who develop PTB. It has been demonstrated that fetal DNA is hypomethylated and is pro-inflammatory. The pro-inflammatory properties of placental-derived DNA, the effects of placental inflammation on the production of cff-DNA, and its significance in the pathogenesis of PTB are unknown.Using a human placental explant model, we analysed the effect of lipopolysaccharide (LPS) stimulation on cff-DNA production, and used the cff-DNA generated by these explants to examine the methylation profile and in-vitro pro-inflammatory properties of cff-DNA. LPS caused significant production of TNF-α from placental explants, but did not significantly increase the cff-DNA production. Placental-derived cff-DNA, was found to have a small proportion of unmethylated CpG motifs, but was more similar to adult DNA than to more highly unmethylated E-coli DNA. However, cff-DNA did not elicit production of inflammatory cytokines (IL-6, IL-8, TNF-α and CXCL10) by peripheral blood mononuclear cells from pregnant women. Furthermore, in contrast to LPS, intra-uterine injections of mouse placental DNA did not decrease time to delivery in an in-vivo mouse PTB model compared to control animals.This study demonstrates that placental inflammation does not increase the production of cff-DNA in placental explants, and cff-DNA alone is not sufficient to elicit an inflammatory response in human PBMC cultures ex-vivo. It also shows that mouse placental DNA does not cause PTB in-vivo. This suggests that cff-DNA might be predominantly an effect of parturition and not a principal causative agent.


2015 ◽  
Vol 43 (5) ◽  
Author(s):  
Marija Hadži-Lega ◽  
Ana Daneva Markova ◽  
Milan Stefanovic ◽  
Mile Tanturovski

AbstractThe aim of this study was to determine the relationship between sonographic cervical length, fetal fibronectin (fFN), phIGFBP-1 (actim partus test), cytokines (IL-6, IL-2R, and TNF-α), and spontaneous preterm birth (SPTB) up to 14 days from sampling.Fifty-eight patients were recruited in a period of 6 months from September 2013 until March 2014 with symptoms or complaints suggestive of preterm labor. Consenting women were treated according to usual hospital protocol, with addition of vaginal swabs taken for fetal fibronectin, phIGFBP-1 (actim partus test) and cervical IL6, IL2R, and TNF-α. The outcome variable was occurrence of preterm delivery within 14 days from the day of hospital admission.Thirty-six patients (62.07%) were delivered within 14 days from admission. Our results indicated that the cervical length significantly inversely correlates with the concentration of IL-6 in the CVF (Spearman’s coefficient R=–0.382, P<0.05). Cervical length also correlated with a positive phIGFBP-1 test, i.e., patients with a positive test had an average cervical length of 18.5±4.63 mm, which is significantly lower than patients with a negative test –23.43±7.39 mm (P=0.003).The studied biochemical markers were only moderately successful in the prediction of preterm delivery.


2015 ◽  
Vol 212 (4) ◽  
pp. 533.e1-533.e9 ◽  
Author(s):  
Fara Behnia ◽  
Sasha E. Parets ◽  
Talar Kechichian ◽  
Huaizhi Yin ◽  
Eryn H. Dutta ◽  
...  

Author(s):  
Myrthe J. C. S. Peelen ◽  
Brenda M. Kazemier ◽  
Anita C. J. Ravelli ◽  
Christianne J. M. de Groot ◽  
Joris A. M. van der Post ◽  
...  

2018 ◽  
Author(s):  
Haley R. Eidem ◽  
Jacob Steenwyk ◽  
Jennifer Wisecaver ◽  
John A. Capra ◽  
Patrick Abbot ◽  
...  

AbstractBackgroundThe integration of high-quality, genome-wide analyses offers a robust approach to elucidating genetic factors involved in complex human diseases. Even though several methods exist to integrate heterogeneous omics data, most biologists still manually select candidate genes by examining the intersection of lists of candidates stemming from analyses of different types of omics data that have been generated by imposing hard (strict) thresholds on quantitative variables, such as P-values and fold changes, increasing the chance of missing potentially important candidates.MethodsTo better facilitate the unbiased integration of heterogeneous omics data collected from diverse platforms and samples, we propose a desirability function framework for identifying candidate genes with strong evidence across data types as targets for follow-up functional analysis. Our approach is targeted towards disease systems with sparse, heterogeneous omics data, so we tested it on one such pathology: spontaneous preterm birth (sPTB).ResultsWe developed the software integRATE, which uses desirability functions to rank genes both within and across studies, identifying well-supported candidate genes according to the cumulative weight of biological evidence rather than based on imposition of hard thresholds of key variables. Integrating 10 sPTB omics studies identified both genes in pathways previously suspected to be involved in sPTB as well as novel genes never before linked to this syndrome. integRATE is available as an R package on GitHub (https://github.com/haleyeidem/integRATE).ConclusionsDesirability-based data integration is a solution most applicable in biological research areas where omics data is especially heterogeneous and sparse, allowing for the prioritization of candidate genes that can be used to inform more targeted downstream functional analyses.


Sign in / Sign up

Export Citation Format

Share Document