Placental transcriptome analysis reveals BMI-dependent gene expression profiles in preeclampsia.
Maternal BMI influences placental gene expression in preeclampsia, with SERPINA3 showing significant changes in obese pregnancies.
Where it sits
this study against the rest of the follistatin-344 corpusSummary and findings
This study investigated the association between maternal BMI and placental gene expression patterns in preeclampsia. The analysis included 132 placentas and identified differential expression of several genes across BMI categories. SERPINA3 showed an estimated eight-fold increase in expression in preeclamptic pregnancies complicated by obesity.
Abstract
<h4>Background</h4>Maternal obesity is a well-established risk factor for preeclampsia; however, whether increased maternal BMI is associated with biologically distinct subtypes of this disorder remains unknown.<h4>Objective</h4>To investigate whether maternal BMI is associated with differences in placental gene expression patterns observed in preeclampsia and to identify transcriptomic signatures with potential relevance for future biomarker research.<h4>Study design</h4>This exploratory analysis used placental transcriptomic data obtained from the Gene Expression Omnibus. Differential expression within prespecified contrasts encoding preeclampsia status and maternal BMI was analyzed using a multivariable linear modeling framework with adjustment for relevant confounders. In a secondary analysis, maternal BMI was modeled continuously with an interaction term between BMI and preeclampsia status.<h4>Results</h4>Placental transcriptomic data from 132 placentas representing a range of maternal hypertensive and normotensive states were analyzed. Genes commonly associated with preeclampsia, including FLT1, LEP, HTRA4, and FSTL3, were differentially expressed across all BMI categories. SERPINA3 demonstrated the strongest differential expression in the obese contrast, with an estimated eight-fold increase (95% CI: 3.9-16.6) in preeclamptic pregnancies complicated by obesity, whereas expression differences were smaller and not statistically significant in healthy-weight and overweight contrasts. Gene set enrichment analysis suggested heterogeneity in the underlying biology of preeclampsia across BMI strata.<h4>Conclusion</h4>Placental transcriptional patterns associated with preeclampsia differed across maternal BMI strata. These findings are consistent with previously proposed molecular subtypes of preeclampsia and highlight SERPINA3 as a candidate transcriptomic marker warranting further investigation, specifically in pregnancies complicated by obesity.
Background
Maternal obesity is a well-established risk factor for preeclampsia, but the relationship between increased maternal BMI and distinct subtypes of preeclampsia is not fully understood. Prior research has indicated that gene expression patterns may vary in relation to BMI in preeclamptic pregnancies. This study aims to explore these potential differences and identify relevant transcriptomic signatures that could inform future biomarker research.
Methods
This exploratory analysis utilized placental transcriptomic data from the Gene Expression Omnibus, involving 132 placentas. Differential expression was analyzed using a multivariable linear modeling framework, with adjustments for relevant confounders. Maternal BMI was modeled continuously, including an interaction term between BMI and preeclampsia status.
Results
The primary finding indicates that SERPINA3 showed an estimated eight-fold increase (95% CI: 3.9-16.6) in expression in preeclamptic pregnancies complicated by obesity. Other genes associated with preeclampsia were differentially expressed across all BMI categories, but expression differences in healthy-weight and overweight contrasts were smaller and not statistically significant.
Interpretation
These findings suggest that there may be biologically distinct subtypes of preeclampsia related to maternal BMI, aligning with previously proposed molecular subtypes. While the effect size for SERPINA3 is notable, the clinical significance remains to be established, particularly given the exploratory nature of the study and reliance on transcriptomic data. The study's observational design and potential confounding factors limit the ability to draw definitive conclusions.
Key findings
- SERPINA3 demonstrated an estimated eight-fold increase (95% CI: 3.9-16.6) in preeclamptic pregnancies complicated by obesity.
- Genes commonly associated with preeclampsia, including FLT1, LEP, HTRA4, and FSTL3, were differentially expressed across all BMI categories.
- Expression differences in healthy-weight and overweight contrasts were smaller and not statistically significant.
Limitations
- exploratory analysis with observational data
- small sample size of 132 placentas
- reliance on transcriptomic data, not clinical outcomes
- expression differences in healthy-weight and overweight not statistically significant