Abstract
Abstract
Background
Non-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines.
Results
We confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual’s methylation status is associated with the mother’s age and socioeconomic status, but not with the individual’s own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood.
Conclusions
These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.
Funder
Academy of Finland
academy of finland
the Social Insurance Institution of Finland
Tampere University Hospital Medical Funds
Kuopio, Tampere, and Turku University Hospital Medical Funds
Juho Vainion Säätiö
Paavo Nurmen Säätiö
Sydäntutkimussäätiö
Suomen Kulttuurirahasto
Tampereen Tuberkuloosisäätiö
Emil Aaltosen Säätiö
Yrjö Jahnssonin Säätiö
Signe ja Ane Gyllenbergin Säätiö
Diabetesliitto
the Tampere University Hospital Supporting Foundation
the Finnish Society of Clinical Chemistry
Horizon 2020
European Research Council
Foundation of Clinical Chemistry
Laboratoriolääketieteen edistämissäätiö sr.
Orionin Tutkimussäätiö
the Paulo Foundation
Deutsches Forschungszentrum für Gesundheit und Umwelt, Helmholtz Zentrum München
German Federal Ministry of Education and Research
State of Bavaria
German Research Foundation
Joint Programming Initiative A healthy diet for a healthy life
Publisher
Springer Science and Business Media LLC
Subject
Genetics(clinical),Developmental Biology,Genetics,Molecular Biology
Cited by
14 articles.
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