부산대학교 도서관

Introduction: Twin-twin transfusion syndrome (TTTS) affects 10-15% of monochorionic pregnancies with high morbidity and mortality. Cardiomyopathy affects 70% of early and 100% of advanced TTTS recipients. The etiology of TTTS is unknown and the diagnosis is fraught with challenges. microRNAs (miRs) are small noncoding RNA-molecules that regulate gene expression and are useful biomarkers, including in pediatric heart failure. Hypothesis: We hypothesized that amniotic fluid (AF) miRs could provide novel insights into the pathophysiology and serve as a biomarker of TTTS. We sought to (1) isolate AF miRs, and (2) compare AF miR profiles in advanced TTTS to normal controls. Methods: AF from 10 recipient fetuses with TTTS cardiomyopathy (Cincinnati stage IIIC) and 10 gestational age (GA) and sex-matched normal singleton controls was obtained. Total RNA was extracted using the miRNeasy Mini Kit (Qiagen). miR expression analysis was performed with the Taqman array human miRNA card (Invitrogen). Array data were analyzed with Expression Suite Software (Invitrogen). Random forest (RF) analysis was performed to distinguish the groups. Basic statistic Welch t-test identified statistically significant miRs. Results: Median GA were 19.7 and 19.4 weeks for TTTS and controls, respectively. Six controls and 6 twins were male. Among the TTTS cohort, 0 recipients and 3 donors died before delivery. Based on RF analysis, many miRs were differentially expressed (87 miRs, p <0.0001). The top 3 differentially expressed miRs were hsa-mir-127, hsa-mir-375 and hsa-miR-134 (Figure). Conclusions: Highly significant perturbations exist in AF miR profiles in TTTS cardiomyopathy. AF miRs have potential as promising biomarkers in TTTS. miR-127 regulates genes important in placental formation and may be integral in TTTS development. Validation of AF miR differences in a larger population is underway. [ABSTRACT FROM AUTHOR]