Relationship between apoptosis gene DNA methylation and fetal growth and development

IF 2.4 3区生物学 Q2 GENETICS & HEREDITY Gene Pub Date : 2025-03-15 Epub Date: 2025-01-07 DOI:10.1016/j.gene.2025.149224

Weiwei Wu , Bole Zhang , Jing Zhao , Weixuan Hu , Yulin Li , Yongliang Feng , Yawei Zhang , Suping Wang

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Abstract

Objective

To investigate the relationship between DNA methylation of cord blood apoptosis genes and low birth weight (LBW).

Methods

A case-control study was conducted on 50 pairs of LBW neonates and normal birth weight. Genome-wide methylation assay was performed using Illumina Human Methylation EPIC microarray to analyze the methylation sites of apoptosis-related genes BCL-2, CASP3, and CASP8. The mRNA level of apoptosis gene was verified by RT-qPCR.

Results

Three CpG sites of BCL-2 and three CpG sites of CASP3 were different between the LBW and NBW groups. Logistic regression showed that higher methylation of BCL-2 CpG sites cg12459502 (OR = 1.208, 95% CI:1.029, 1.418) and cg25059899 (OR = 1.193, 95% CI:1.019, 1.395) increased LBW risk, while cg22152050 was protective (OR = 0.589, 95% CI:0.424, 0.820). Stratified analysis confirmed this. Maternal pre-pregnancy BMI positively correlated with BCL-2 methylation (cg12459502, cg25059899) (b = 0.431, 95% CI: 0.027, 0.835; b = 0.494, 95% CI: 0.141, 0.848), while excessive pregnancy weight gain negatively correlated with cg12459502 methylation (b = −0.269, 95% CI: −0.525, −0.013). The results showed that the mRNA level of BCL-2 in NBW group was significantly higher than that in LBW group (P-value < 0.0001).

Conclusion

The DNA methylation levels of BCL-2 and CASP3 genes are associated with fetal growth and development. Additionally, maternal pre-pregnancy BMI and weight gain during pregnancy were found to correlate with BCL-2 methylation, indicating potential epigenetic mechanisms influencing fetal growth.

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凋亡基因DNA甲基化与胎儿生长发育的关系。

目的：探讨脐带血凋亡基因DNA甲基化与低出生体重（LBW）的关系。方法：对50对出生体重正常的低体重新生儿进行病例对照研究。使用Illumina人甲基化EPIC芯片进行全基因组甲基化分析，分析凋亡相关基因BCL-2、CASP3和CASP8的甲基化位点。RT-qPCR检测凋亡基因mRNA表达水平。结果：LBW组与NBW组BCL-2的三个CpG位点和CASP3的三个CpG位点存在差异。逻辑回归表明,更高的bcl - 2 CpG甲基化网站cg12459502(或 = 1.208,95 % CI: 1.029, 1.418)和cg25059899(或 = 1.193,95 % CI: 1.019, 1.395)激光焊的风险增加,而cg22152050保护(或 = 0.589,95 % CI: 0.424, 0.820)。分层分析证实了这一点。孕妇孕前BMI与BCL-2甲基化呈正相关（cg12459502, cg25059899） (b = 0.431,95 %CI: 0.027, 0.835；b = 0.494,95 %CI: 0.141, 0.848)，而孕期体重过度增加与cg12459502甲基化呈负相关（b = -0.269,95 %CI: -0.525, -0.013）。结果显示，NBW组BCL-2 mRNA水平显著高于LBW组（P ）。结论：BCL-2和CASP3基因的DNA甲基化水平与胎儿生长发育有关。此外，孕妇孕前BMI和孕期体重增加被发现与BCL-2甲基化相关，表明影响胎儿生长的潜在表观遗传机制。

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来源期刊

Gene 生物-遗传学

CiteScore

6.10

自引率

2.90%

发文量

718

审稿时长

42 days

期刊介绍： Gene publishes papers that focus on the regulation, expression, function and evolution of genes in all biological contexts, including all prokaryotic and eukaryotic organisms, as well as viruses.