Plasma microRNA signature of alcohol consumption: the Rotterdam Study.

BACKGROUND: MicroRNAs (miRNAs) represent a class of non-coding RNAs that regulate gene expression and are implicated in the pathogenesis of different diseases. Alcohol consumption might affect the expression of miRNAs, which in turn could play a role in risk of diseases.

OBJECTIVE: We investigated whether plasma concentrations of miRNAs are altered by alcohol consumption. Given the existing evidence showing the link between alcohol and liver diseases, we further explored the extent to which these associations are mediated by miRNAs.

DESIGN: Profiling of plasma miRNAs was conducted using HTG EdgeSeq miRNA Whole Transcriptome Assay in 1933 participants of the Rotterdam Study. Linear regression was implemented to explore the link between alcohol consumption (glasses/day) and miRNAs levels, adjusted for age, sex, cohort, BMI, and smoking. Sensitivity analysis for alcohol-categories (non-, light-, and heavy-drinkers) was performed, where light drinkers-corresponded to 0←≤2 glasses/day in men; 0←≤1 glasses/day in women and heavy→2 glasses/day in men; >1 glasses/day in women. Moreover, we utilized the alcohol-associated miRNAs to explore their potential mediatory role between alcohol consumption and liver-related traits. Finally, we retrieved putative target genes of identified miRNAs to gain an understanding of the molecular pathways concerning alcohol consumption.

RESULTS: Plasma levels of miR-193b-3p, miR-122-5p, miR-3937, and miR-4507 were significantly associated with alcohol consumption surpassing the Bonferroni-corrected P-value< 8.46×10-5. The top significant association was observed for miR-193b-3p (β = 0.087, P-value = 2.90×10-5). Furthermore, a potential mediatory role of miR-3937 and miR-122-5p was observed between alcohol consumption and liver traits. Pathway analysis of putative target genes revealed involvement in biological regulation and the cellular processes.

CONCLUSIONS: This study indicates that alcohol consumption is associated with plasma concentrations of four miRNAs. We outline a potential mediatory role of two alcohol-associated miRNAs (miR-3937 and miR-122-5p), laying the groundwork for further exploration of miRNAs as potential mediators between lifestyle factors and disease development.