Using Residual Newborn Blood Spots to Investigate CpG Methylation in Relation to Air Pollution and Congenital Heart Defects

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2025-04-23 DOI:10.1002/bdr2.2473

Thomas J. Luben, Kyle Roell, Cailee E. Harrington, Jeanette A. Stingone, Cavin K. Ward-Caviness, Tania A. Desrosiers, Rebecca C. Fry, Andrew F. Olshan

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引用次数: 0

Abstract

Background

The prevalence of tetralogy of Fallot (TOF), a common congenital heart defect, has increased over the last two decades.

Methods

Genome-wide CpG methylation patterns were assessed and analyzed in relation to gestational air pollution exposure among 24 infants with TOF and 24 sex-matched control infants without a birth defect from a North Carolina population-based, case–control study of major structural birth defects (2006–2011). Air pollution exposure during obstetric weeks 3–8 was assigned based on self-reported residence. DNA was extracted from residual newborn blood spots, and DNA methylation levels were measured using the Illumina EPIC Array.

Results

Cases had higher exposure to both PM₂_.5 and O₃ compared to controls. No specific CpG loci were statistically significantly associated with TOF status or air pollution exposure; however, we observed associations between TOF case status and DNA methylation at specific genomic regions with genes enriched for functions in metabolism. Additionally, there were significant regions that displayed differential DNA methylation in relation to air pollution exposure within genes involved in apoptosis, necrosis, inflammation, and immune response pathways.

Conclusions

Generally, air pollution exposure and TOF were associated with differential DNA methylation in distinct genes. These results highlight suggestive links between the environment, epigenome, and TOF to be further investigated in larger studies.

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利用新生儿残留血斑研究CpG甲基化与空气污染和先天性心脏缺陷的关系

法洛四联症（TOF）是一种常见的先天性心脏缺陷，其患病率在过去二十年中有所增加。方法评估和分析了24名TOF婴儿和24名性别匹配的无出生缺陷婴儿的全基因组CpG甲基化模式与妊娠期空气污染暴露的关系，这些婴儿来自北卡罗来纳州一项基于人群的主要结构性出生缺陷病例对照研究（2006-2011）。分娩3-8周期间的空气污染暴露是根据自我报告的住所进行分配的。从新生儿残余血斑中提取DNA，使用Illumina EPIC Array检测DNA甲基化水平。结果病例PM2.5和O3暴露量均高于对照组。没有特定的CpG基因位点与TOF状态或空气污染暴露有统计学意义上的显著关联；然而，我们观察到TOF病例状态与特定基因组区域的DNA甲基化之间存在关联，这些区域富含代谢功能的基因。此外，在涉及细胞凋亡、坏死、炎症和免疫反应途径的基因中，存在与空气污染暴露相关的显著DNA甲基化区域。结论总的来说，空气污染暴露和TOF与不同基因的差异DNA甲基化有关。这些结果强调了环境、表观基因组和TOF之间的联系，需要在更大规模的研究中进一步研究。

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来源期刊

Birth Defects Research Medicine-Embryology

CiteScore

3.60

自引率

9.50%

发文量

153

期刊介绍： The journal Birth Defects Research publishes original research and reviews in areas related to the etiology of adverse developmental and reproductive outcome. In particular the journal is devoted to the publication of original scientific research that contributes to the understanding of the biology of embryonic development and the prenatal causative factors and mechanisms leading to adverse pregnancy outcomes, namely structural and functional birth defects, pregnancy loss, postnatal functional defects in the human population, and to the identification of prenatal factors and biological mechanisms that reduce these risks. Adverse reproductive and developmental outcomes may have genetic, environmental, nutritional or epigenetic causes. Accordingly, the journal Birth Defects Research takes an integrated, multidisciplinary approach in its organization and publication strategy. The journal Birth Defects Research contains separate sections for clinical and molecular teratology, developmental and reproductive toxicology, and reviews in developmental biology to acknowledge and accommodate the integrative nature of research in this field. Each section has a dedicated editor who is a leader in his/her field and who has full editorial authority in his/her area.