ABSTRACT

Adverse pregnancy outcomes disproportionately affect non-Hispanic (NH) Black patients in the United States. Structural racism has been associated with increased psychosocial distress and inflammation and may trigger oxidative stress. Thus, the nitric oxide (NO) pathway (involved in the regulation of inflammation and oxidative stress) may partly explain the underlying disparities in obstetric outcomes.

Cohort study of 154 pregnant patients with high-risk obstetric histories; n = 212 mRNAs and n = 108 microRNAs (miRNAs) in the NO pathway were evaluated in circulating white blood cells. NO pathway mRNA and miRNA transcript counts were compared by self-reported race; NH Black patients were compared with women of other races/ethnicities. Finally, miRNA-mRNA expression levels were correlated.

Twenty-two genes (q < 0.10) were differentially expressed in self-identified NH Black individuals. Superoxide dismutase 1 (SOD1), interleukin-8 (IL-8), dynein light chain LC8-type 1 (DYNLL1), glutathione peroxidase 4 (GPX4), and glutathione peroxidase 1 (GPX1) were the five most differentially expressed genes among NH Black patients compared to other patients. There were 63 significantly correlated miRNA-mRNA pairs (q < 0.10) demonstrating potential miRNA regulation of associated target mRNA expression. Ten miRNAs that were identified as members of significant miRNA-mRNA pairs were also differentially expressed among NH Black patients (q < 0.10).

These findings support an association between NO pathway and inflammation and infection-related mRNA and miRNA expression in blood drawn during pregnancy and patient race/ethnicity. These findings may reflect key differences in the biology of inflammatory gene dysregulation that occurs in response to the stress of systemic racism and that underlies disparities in pregnancy outcomes.

摘要

在美国，不良妊娠结局对非西班牙裔 (NH) 黑人患者的影响尤为严重。结构性种族主义与社会心理困扰和炎症增加有关，并可能引发氧化应激。因此，一氧化氮 (NO) 途径（参与炎症和氧化应激的调节）可能部分解释了产科结果的潜在差异。

对 154 名有高危产科病史的孕妇的队列研究；在循环白细胞中评估了 NO 通路中的 n = 212 个 mRNA 和 n = 108 个 microRNA (miRNA)。通过自我报告的种族比较 NO 通路 mRNA 和 miRNA 转录物计数；NH Black 患者与其他种族/族裔的女性进行了比较。最后，将 miRNA-mRNA 表达水平相关联。

22 个基因 (q < 0.10) 在自我识别的 NH Black 个体中差异表达。超氧化物歧化酶 1 ( SOD1 )、白细胞介素 8 ( IL-8 )、动力蛋白轻链 LC8 型 1 ( DYNLL1 )、谷胱甘肽过氧化物酶 4 ( GPX4 ) 和谷胱甘肽过氧化物酶 1 ( GPX1 )是 NH 中表达差异最大的五个基因黑人患者与其他患者相比。有 63 个显着相关的 miRNA-mRNA 对 (q < 0.10)，证明了相关靶 mRNA 表达的潜在 miRNA 调节。被鉴定为重要 miRNA-mRNA 对成员的 10 个 miRNA 在 NH Black 患者中也有差异表达 (q < 0.10)。

这些发现支持 NO 通路与炎症和感染相关的 mRNA 和 miRNA 表达在怀孕期间抽取的血液和患者种族/民族之间的关联。这些发现可能反映了炎症基因失调生物学的关键差异，炎症基因失调是对系统性种族主义压力的反应，也是妊娠结果差异的基础。