Nowak Alexandra L, Saadat Nadia, Sun Jiao, Forsman Anna M, Liang Xiaoyu, Joyce Cara, Woo Jennifer, Engeland Christopher G, Misra Dawn P, Giurgescu Carmen, Zhang Wei, Anderson Cindy M
Marcella Niehoff School of Nursing, Loyola University at Chicago, Maywood, IL, USA.
Department of Paediatrics, University of Michigan, Ann Arbor, MI, USA.
Biol Res Nurs. 2025 Apr;27(2):205-215. doi: 10.1177/10998004241275049. Epub 2024 Oct 23.
Preterm birth (PTB; <37 weeks completed gestation) is a devastating problem affecting over 13 million live births worldwide. In the U.S., African Americans experience significantly higher rates of PTB compared to non-Hispanic Whites. PTB disparities have been linked to social determinants of health (e.g., socioeconomic status, discrimination). However, the biological underpinnings related to these associations are unclear. DNA methylation (DNAm) is subject to environmental influences, and DNAm modifications are known to affect gene expression. Using a multi-omic approach, we examined differences in combined DNA methylation (DNAm) and messenger RNA (mRNA) transcriptomic data from 20 pregnant African American women (12 PTB; 8 term birth) early in pregnancy (8-18 weeks gestation). We found that the gene was both differentially methylated (cg12296550; = .02) and differentially expressed ( = .014; log2FC = 2.5) between women with PTB and term birth. Gene expression analysis showed and ( = .028; log2FC = -3.6) were the two most highly expressed genes. expressed higher in PTB and expressed higher in term birth. However, no genes remained significant ( < .05) after Bonferroni correction. and were identified as a potential biomarkers in dimensionality reduction models and are also important to immune function and allogenic breakdown. Altered gene expression may lead to inflammatory imbalances or allogenic intolerance resulting in PTB. This study provides proof-of-concept evidence for the feasibility and importance of future multi-omics studies with larger populations to further explore the genes and pathways identified here.
早产(PTB;妊娠不足37周)是一个严重的问题,影响着全球超过1300万例活产。在美国,与非西班牙裔白人相比,非裔美国人的早产率显著更高。早产差异与健康的社会决定因素(如社会经济地位、歧视)有关。然而,与这些关联相关的生物学基础尚不清楚。DNA甲基化(DNAm)受环境影响,已知DNAm修饰会影响基因表达。我们采用多组学方法,研究了20名非裔美国孕妇(12例早产;8例足月产)在妊娠早期(妊娠8至−18周)的联合DNA甲基化(DNAm)和信使核糖核酸(mRNA)转录组数据的差异。我们发现,早产和足月产女性之间,该基因的甲基化存在差异(cg12296550;P = 0.02),表达也存在差异(P = 0.014;log2倍变化 = 2.5)。基因表达分析显示,基因1和基因2(P = 0.028;log2倍变化 = −3.6)是两个表达水平最高的基因。基因1在早产中表达较高,基因2在足月产中表达较高。然而,经Bonferroni校正后,没有基因仍具有显著性(P < 0.05)。在降维模型中,基因1和基因2被确定为潜在的生物标志物,对免疫功能和同种异体分解也很重要。基因表达改变可能导致炎症失衡或同种异体不耐受,从而导致早产。本研究为未来开展更大规模人群的多组学研究以进一步探索此处鉴定的基因和途径的可行性和重要性提供了概念验证证据。