Placental microRNA methylome signatures may serve as biomarkers and therapeutic targets for prenatally opioid-exposed infants with neonatal opioid withdrawal syndrome

胎盘 microRNA 甲基化特征可作为产前阿片类药物暴露婴儿患新生儿阿片类药物戒断综合征的生物标志物和治疗靶点

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作者:Uppala Radhakrishna, Swapan K Nath, Lavanya V Uppala, Avinash Veerappa, Ariadna Forray, Srinivas B Muvvala, Raghu P Metpally, Richard C Crist, Wade H Berrettini, Lori M Mausi, Sangeetha Vishweswaraiah, Ray O Bahado-Singh

Conclusion

This is the first study to analyze miRNA methylation profiles in NOWS infants and illustrates the unique role miRNAs might have in diagnosing and treating the disease. Furthermore, these data may provide a step toward feasible precision medicine for NOWS babies as well.

Methods

The Illumina Infinium Methylation EPIC BeadChip was used to analyze DNA methylation levels of miRNA-encoding genes in 96 human placental tissues to identify miRNA gene methylation profiles as-sociated with NOWS: 32 from mothers whose prenatally opioid-exposed infants required pharmacologic management for NOWS, 32 from mothers whose prenatally opioid-exposed infants did not require treat-ment for NOWS, and 32 unexposed controls.

Results

The study identified 46 significantly differentially methylated (FDR p-value ≤ 0.05) CpGs associated with 47 unique miRNAs, with a receiver operating characteristic (ROC) area under the curve (AUC) ≥0.75 including 28 hypomethylated and 18 hypermethylated CpGs as potentially associated with NOWS. These dysregulated microRNA methylation patterns may be a contributing factor to NOWS pathogenesis.

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