Abstract
BACKGROUND: MicroRNAs (miRNAs) represent a class of noncoding 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. OBJECTIVES: 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. METHODS: Profiling of plasma miRNAs was conducted using the 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/d) and miRNA concentrations, adjusted for age, sex, cohort, BMI, and smoking. Sensitivity analysis for alcohol categories (nondrinkers, light drinkers, and heavy drinkers) was performed, where light drinkers corresponded to 0-2 glasses/d in men and 0-1 glasses/d in women, and heavy drinkers to >2 glasses/d in men and >1 glass/d 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 concentrations of miR-193b-3p, miR-122-5p, miR-3937, and miR-4507 were significantly associated with alcohol consumption surpassing the Bonferroni-corrected P < 8.46 × 10-5. The top significant association was observed for miR-193b-3p (β = 0.087, P = 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 cellular processes. CONCLUSIONS: This study indicates that alcohol consumption is associated with plasma concentrations of 4 miRNAs. We outline a potential mediatory role of 2 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.
| Original language | English |
|---|---|
| Pages (from-to) | 2677-2688 |
| Number of pages | 12 |
| Journal | The Journal of nutrition |
| Volume | 152 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - Dec 2022 |
Bibliographical note
Funding Information:The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University; Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. miRNA expression analyses by HTG EdgeSeq WTA were funded by Johnson & Johnson. The authors’ responsibilities were as follows—IK and MG: conceived and designed the study and wrote the original draft; MAI and RJDK: performed the investigation and data curation; IK: analyzed the data, performed the statistical analyses, and had primary responsibility for the final content; IK, MG, SCEM, DB, JL, and TV: interpreted the results; IK, MG, TV, DB, SCEM, and YA: reviewed and edited the manuscript; and all authors: read and approved the final manuscript. Data used in this article will not be made available because of the confidential nature of the data collected; analytic code will be made available upon reasonable request to the corresponding author. The authors reported no funding received for this study. Author disclosures: the authors report no conflicts of interest. Supplemental Tables 1–8 are available from the “Supplementary data” link in the online posting of the article and from the same link in the online table of contents at https://academic.oup.com/jn/. YA and SCEM contributed equally to this work.
Funding Information:
The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University; Netherlands Organization for Health Research and Development (ZonMw); the Research Institute for Diseases in the Elderly (RIDE); the Ministry of Education, Culture and Science; the Ministry for Health, Welfare and Sports; the European Commission (DG XII); and the Municipality of Rotterdam. miRNA expression analyses by HTG EdgeSeq WTA were funded by Johnson & Johnson. The authors’ responsibilities were as follows—IK and MG: conceived and designed the study and wrote the original draft; MAI and RJDK: performed the investigation and data curation; IK: analyzed the data, performed the statistical analyses, and had primary responsibility for the final content; IK, MG, SCEM, DB, JL, and TV: interpreted the results; IK, MG, TV, DB, SCEM, and YA: reviewed and edited the manuscript; and all authors: read and approved the final manuscript.
Publisher Copyright:
© 2022 American Society for Nutrition.