Maternal serum Lamin A is a potential biomarker that can predict adverse pregnancy outcomes

Chen, Lizhu; Xiu, Yun; Wu, Qi‐Jun; Wang, Yu; Zhang, Yixin; Xue, Jianming; Wang, Qinbo; Yuan, Zhengwei

doi:10.1016/j.ebiom.2022.103932

Cited by 5 publications

(6 citation statements)

References 33 publications

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“…We identified cg09820673 located at 3′ UTR to be significantly lower in individuals with hypoplastic left heart syndrome ( β : −.28; FDR p ‐value: 0.006) compared to other CHD subtypes (Figure 1a). Prior studies have reported varied gene expression of LMNA between CHD subtypes of pulmonary stenosis and vascular ring (Chen et al, 2022). Whether such transcriptomic differences are a consequence of altered methylation needs to be ascertained in future experimental investigations.…”

Section: Discussionmentioning

confidence: 99%

“…Previous epigenome‐wide analyses do not highlight LMNA DNAm among their top findings; variations in disease severity, the timing of blood collection, and limited sample sizes may contribute to these differences. However, maternal Lamin A gene expression and protein levels are reported as robust biomarkers of offspring CHD with severely downregulated LMNA transcription in mothers with offspring CHD and lower levels of LMNA in fetal CHD heart (Chen et al, 2016, 2022). Our finding provides initial evidence of the role of LMNA DNAm in CHD with the potential to inform targeted prevention strategies to reduce CHD risk (Wu & Zhang, 2014).…”

Section: Discussionmentioning

confidence: 99%

“…Few studies have identified associations of LMNA mutations with CHD (Baban et al, 2020; Heller et al, 2017). Interestingly, maternal serum levels of LMNA are strongly correlated with CHD, highlighting its potential as a prenatal diagnostic biomarker (Chen et al, 2016; Chen et al, 2022). However, whether LMNA DNAm is involved in CHD remains unknown.…”

Section: Introductionmentioning

confidence: 99%

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DNA methylation of the Lamin A/C gene is associated with congenital heart disease

Mukherjee,

Bolin,

Qasim

et al. 2024

Birth Defects Research

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BackgroundPrior studies report associations of maternal serum Lamin A, encoded by the LMNA gene, with fetal congenital heart disease (CHD). It is unknown whether DNA methylation (DNAm) of cytosine‐phosphate‐guanine (CpG) sites in LMNA impacts the CHD susceptibility.MethodsWe investigated the associations of LMNA DNAm with CHD using publicly available data of CHD cases (n = 197) and controls (n = 134) from the Gene Expression Omnibus repository. Peripheral blood DNAm was measured using Illumina 850 K BeadChip for cases and 450 K BeadChip for controls. We tested 31 LMNA CpGs to identify differences in DNAm between cases and controls using linear regression correcting for multiple testing with false discovery rate (FDR). In a case‐only analysis, we tested the variations in LMNA DNAm between CHD subtypes. To identify the consistency of DNAm across tissue types we compared peripheral blood (n = 197) and heart tissue DNAm (n = 20) in CHD cases.ResultsAfter adjusting for age, sex, and cell types there were significant differences in 17 of the 31 LMNA CpGs between CHD cases and controls (FDR p ≤ .05). We identified lower DNAm of cg09820673 at 3′ UTR for hypoplastic left heart syndrome compared to other CHD subtypes. Three CpGs exhibited uniform DNAm in blood and heart tissues in cases. Eleven CpGs showed changes in the same direction in blood and heart tissues in cases compared to controls.ConclusionWe identify statistically significant differences in LMNA DNAm between CHD cases and controls. Future studies should investigate the role of maternal LMNA DNAm in CHD development.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA methylation of the Lamin A/C gene is associated with congenital heart disease

Mukherjee,

Bolin,

Qasim

et al. 2024

Birth Defects Research

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“…Therefore, prenatal diagnosis of CHD not only prepares the parents and medical staff for treatment after birth but also allows early intervention and may yield a better prognosis. Several hematological biomarkers, including PAPP-A, free b-HCG, natriuretic peptide, and chromosome microarray analysis, have potential value in the early detection of CHD (Miyoshi et al, 2018;Wang et al, 2018b;Alanen et al, 2019;Gu et al, 2019;Bahado-Singh et al, 2020;Chen et al, 2022). In this study, performed in two groups from two different hospitals, we collected plasma samples from first-trimester pregnant women carrying fetuses with or without CHD.…”

Section: Discussionmentioning

confidence: 99%

Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease

Yin,

Cao,

Wang

et al. 2023

EMBO Mol Med

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Prenatal diagnosis of congenital heart disease (CHD) relies primarily on fetal echocardiography conducted at mid‐gestational age—the sensitivity of which varies among centers and practitioners. An objective method for early diagnosis is needed. Here, we conducted a case–control study recruiting 103 pregnant women with healthy offspring and 104 cases with CHD offspring, including VSD (42/104), ASD (20/104), and other CHD phenotypes. Plasma was collected during the first trimester and proteomic analysis was performed. Principal component analysis revealed considerable differences between the controls and the CHDs. Among the significantly altered proteins, 25 upregulated proteins in CHDs were enriched in amino acid metabolism, extracellular matrix receptor, and actin skeleton regulation, whereas 49 downregulated proteins were enriched in carbohydrate metabolism, cardiac muscle contraction, and cardiomyopathy. The machine learning model reached an area under the curve of 0.964 and was highly accurate in recognizing CHDs. This study provides a highly valuable proteomics resource to better recognize the cause of CHD and has developed a reliable objective method for the early recognition of CHD, facilitating early intervention and better prognosis.

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“…The serum and urinary test results during pregnancy are critical for assessing maternal and fetal health status and predicting adverse postnatal outcomes 16–18 . For example, the high maternal glucose level is an indication of the risk of developing gestational diabetes 19 , and abnormal maternal hemoglobin levels may be a warning of preterm birth 20,21 .…”

Section: Introductionmentioning

confidence: 99%

Genetic analysis of 104 pregnancy phenotypes in 39,194 Chinese women

Xiao,

Li,

Yang

et al. 2023

Preprint

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Maternity is a special period in a woman’s life that involves substantial physiological, psychological, and hormonal changes. These changes may cause alterations in many clinical measurements during pregnancy, which can be used to monitor and diagnose maternal disorders and adverse postnatal outcomes. Exploring the genetic background of these phenotypes is key to elucidating the pathogenesis of pregnancy disorders. In this study, we conducted a large-scale molecular biology analysis of 104 pregnancy phenotypes based on genotype data from 39,194 Chinses women. Genome- wide association analysis identified a total of 407 trait-locus associations, of which 75.18% were previously reported. Among the 101 novel associations for 37 phenotypes, some were potentially pregnancy-specific and worth further experimental investigation. For example,ESR1with fasting glucose, hemoglobin, hematocrit, and several leukocytoses;ZSCAN31with blood urea nitrogen. We further performed pathway- based analysis and uncovered at least one significant pathway for 24 traits, in addition to previously known functional pathways, novel findings included birthweight with “Reactome signaling by NODAL”, twin pregnancy with “Reactome mitotic G1-G1/S phases”. The partitioning heritability analysis recapitulated known trait-relevant tissue/cell types, and also discovered interesting results including twin pregnancy with “embryoid bodies” cell-type enrichment, the delivery type cesarean section with “fallopian tube”, and birth weight with “ovary and embryonic stem cells”. In terms of both sample size and the variety of phenotypes, our work is one of the largest genetic studies of pregnancy phenotypes across all populations. We believe that this study will provide a valuable resource for exploring the genetic background of pregnancy phenotypes and also for further research on pregnancy-related diseases and adverse neonatal outcomes.

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Maternal serum Lamin A is a potential biomarker that can predict adverse pregnancy outcomes

Cited by 5 publications

References 33 publications

DNA methylation of the Lamin A/C gene is associated with congenital heart disease

DNA methylation of the Lamin A/C gene is associated with congenital heart disease

Proteome profiling of early gestational plasma reveals novel biomarkers of congenital heart disease

Genetic analysis of 104 pregnancy phenotypes in 39,194 Chinese women

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