Relationship between apoptosis gene DNA methylation and fetal growth and development

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

doi:10.1016/j.gene.2025.149224

Relationship between apoptosis gene DNA methylation and fetal growth and development

Gene. 2025 Jan 7:149224. doi: 10.1016/j.gene.2025.149224. Online ahead of print.

Authors

Weiwei Wu¹, Bole Zhang², Jing Zhao², Weixuan Hu², Yulin Li², Yongliang Feng², Yawei Zhang³, Suping Wang⁴

Affiliations

¹ Department of Epidemiology, School of Public Health, Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, China; MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, Shanxi, China. Electronic address: [email protected].
² Department of Epidemiology, School of Public Health, Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, China; MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, Shanxi, China.
³ National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China. Electronic address: [email protected].
⁴ Department of Epidemiology, School of Public Health, Center of Clinical Epidemiology and Evidence Based Medicine, Shanxi Medical University, Taiyuan, China; MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, Shanxi, China. Electronic address: [email protected].

PMID: 39788353
DOI: 10.1016/j.gene.2025.149224

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 < 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.

Keywords: Apoptosis; Birth weight; Cord blood; DNA methylation.