Adulthood blood levels of hsa-miR-29b-3p associate with preterm birth and adult metabolic and cognitive health

Abstract

Preterm birth (PTB) is associated with increased risk of type 2 diabetes and neurocognitive impairment later in life. We analyzed for the first time the associations of PTB with blood miRNA levels in adulthood. We also investigated the relationship of PTB associated miRNAs and adulthood phenotypes previously linked with premature birth. Blood MicroRNA profiling, genome-wide gene expression analysis, computer-based cognitive testing battery (CANTAB) and serum NMR metabolomics were performed for Young Finns Study subjects (aged 34-49 years, full-term n=682, preterm n=84). Preterm birth (vs. full-term) was associated with adulthood levels of hsa-miR-29b-3p in a fully adjusted regression model (p=1.90 x 10^-4, FDR=0.046). The levels of hsa-miR-29b-3p were down-regulated in subjects with PTB with appropriate birthweight for gestational age (p=0.002, fold change [FC]=- 1.20) and specifically in PTB subjects with small birthweight for gestational age (p=0.095, FC=- 1.39) in comparison to individuals born full term. Hsa-miR-29b-3p levels correlated with the expressions of its target-mRNAs BCL11A and CS and the gene set analysis results indicated a target-mRNA driven association between hsa-miR-29b-3p levels and Alzheimer's disease, Parkinson's disease, Insulin signaling and Regulation of Actin Cytoskeleton pathway expression. The level of hsa-miR-29b-3p was directly associated with visual processing and sustained attention in CANTAB test and inversely associated with serum levels of VLDL subclass component and triglyceride levels. In conlcusion, adult blood levels of hsa-miR-29b-3p were lower in subjects born preterm. Hsa-miR-29b-3p associated with cognitive function and may be linked with adulthood morbidities in subjects born preterm, possibly through regulation of gene sets related to neurodegenerative diseases and insulin signaling as well as VLDL and triglyceride metabolism.