Relationship between apoptosis gene DNA methylation and fetal growth and development

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.