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

IF 1.6 4区医学 Q4 DEVELOPMENTAL BIOLOGY

Birth Defects Research Pub Date : 2024-07-28 DOI:10.1002/bdr2.2381

Nandini Mukherjee, Elijah H. Bolin, Amna Qasim, Mohammed S. Orloff, Philip J. Lupo, Wendy N. Nembhard

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引用次数: 0

Abstract

Background

Prior 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.

Methods

We 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.

Results

After 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.

Conclusion

We 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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Lamin A/C 基因的 DNA 甲基化与先天性心脏病有关。

背景：先前的研究报告称，由 LMNA 基因编码的母体血清 Lamin A 与胎儿先天性心脏病（CHD）有关。目前还不清楚 LMNA 中胞嘧啶-磷酸鸟嘌呤（CpG）位点的 DNA 甲基化（DNAm）是否会影响先天性心脏病的易感性：我们利用基因表达总库（Gene Expression Omnibus）中公开的 CHD 病例（197 例）和对照组（134 例）数据，研究了 LMNA DNAm 与 CHD 的关系。使用 Illumina 850 K BeadChip 测量病例的外周血 DNAm，使用 450 K BeadChip 测量对照组的外周血 DNAm。我们检测了 31 个 LMNA CpGs，利用线性回归校正多重检测的错误发现率 (FDR)，确定病例和对照组之间 DNAm 的差异。在一项只针对病例的分析中，我们检测了不同 CHD 亚型之间 LMNA DNAm 的差异。为了确定不同组织类型DNAm的一致性，我们比较了CHD病例的外周血（n = 197）和心脏组织DNAm（n = 20）：结果：在对年龄、性别和细胞类型进行调整后，CHD 病例和对照组在 31 个 LMNA CpGs 中的 17 个存在显著差异（FDR p ≤ .05）。与其他 CHD 亚型相比，我们发现左心发育不全综合征 3' UTR 的 cg09820673 DNAm 较低。有三个 CpGs 在病例的血液和心脏组织中显示出一致的 DNAm。与对照组相比，病例的血液和心脏组织中有 11 个 CpGs 显示出相同方向的变化：结论：我们发现 CHD 病例和对照组的 LMNA DNAm 存在明显的统计学差异。今后的研究应探讨母体 LMNA DNAm 在 CHD 发病中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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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.