A1 Vertaisarvioitu alkuperäisartikkeli tieteellisessä lehdessä
Regulation of nc886 (vtRNA2-1) RNAs is associated with cardiometabolic risk factors and diseases
Tekijät: Rajić, Sonja; Delerue, Thomas; Ronkainen, Justiina; Zhang, Ruiyuan; Ciantar, Joanna; Kostiniuk, Daria; Mishra, Pashupati P.; Lyytikäinen, Leo-Pekka; Mononen, Nina; Kananen, Laura; Peters, Annette; Winkelmann, Juliane; Kleber, Marcus E.; Lorkowski, Stefan; Kähönen, Mika; Lehtimäki, Terho; Raitakari, Olli; Waldenberger, Melanie; Gieger, Christian; März, Winfried; Harville, Emily W.; Sebert, Sylvain; Marttila, Saara; Raitoharju, Emma
Kustantaja: Springer Science and Business Media LLC
Kustannuspaikka: LONDON
Julkaisuvuosi: 2025
Journal: Clinical Epigenetics
Tietokannassa oleva lehden nimi: Clinical Epigenetics
Lehden akronyymi: CLIN EPIGENETICS
Artikkelin numero: 68
Vuosikerta: 17
Numero: 1
Sivujen määrä: 15
ISSN: 1868-7075
eISSN: 1868-7083
DOI: https://doi.org/10.1186/s13148-025-01871-7
Verkko-osoite: https://doi.org/10.1186/s13148-025-01871-7
Rinnakkaistallenteen osoite: https://research.utu.fi/converis/portal/detail/Publication/498472758
Non-coding 886 (nc886, vtRNA2-1) is a polymorphically imprinted gene. The methylation status of this locus has been shown to be associated with periconceptional conditions, and both the methylation status and the levels of nc886 RNAs have been shown to associate with later-life health traits. We have previously shown that nc886 RNA levels are associated not only with the methylation status of the locus, but also with a genetic polymorphism upstream from the locus. In this study, we describe the genetic and epigenetic regulators that predict lifelong nc886 RNA levels, as well as their association with cardiometabolic disease (CMD) risk factors and events. We utilised six population cohorts and one CMD cohort comprising 9058 individuals in total. The association of nc886 RNA levels, as predicted by epigenetic and genetic regulators, with CMD phenotypes was analysed using regression models, with a meta-analysis of the results. The meta-analysis showed that individuals with upregulated nc886 RNA levels have higher diastolic blood pressure (beta = 0.07, p = 0.008), lower HDL levels (beta = - 0.07, p = 0.006) and an increased incidence of type 2 diabetes (OR = 1.260, p = 0.013). Moreover, CMD patients with upregulated nc886 RNA levels have an increased incidence of stroke (OR = 1.581, p = 0.006) and death (OR = 1.290, p = 0.046). In conclusion, we show that individuals who are predicted to present elevated nc886 RNA levels have poorer cardiovascular health and are at an elevated risk of complications in secondary prevention. This unique mechanism yields metabolic variation in human populations, constituting a CMD risk factor that cannot be modified through lifestyle choices.
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Julkaisussa olevat rahoitustiedot:
Open access funding provided by Tampere University (including Tampere University Hospital). The Young Finns Study has been financially supported by the following organisations: the Academy of Finland (grants 356405, 322098, 286284, 134309 (Eye), 126925, 121584, 124282, 129378 [Salve], 117797 [Gendi] and 141071 [Skidi]); the Social Insurance Institution of Finland; Competitive State Research Financing of the Expert Responsibility area of Kuopio, Tampere and Turku University Hospitals (grant X51001); the Juho Vainio Foundation; the Paavo Nurmi Foundation; the Finnish Foundation for Cardiovascular Research; the Finnish Cultural Foundation; the Sigrid Juselius Foundation; the Tampere Tuberculosis Foundation; the Emil Aaltonen Foundation; the Yrjö Jahnsson Foundation; the Signe and Ane Gyllenberg Foundation; the Diabetes Research Foundation of the Finnish Diabetes Association; EU Horizon 2020 (grant 755320 for TAXINOMISIS and grant 848146 for To Aition); the European Research Council (grant 742927 for MULTIEPIGEN project); the Tampere University Hospital Supporting Foundation; the Finnish Society of Clinical Chemistry; the Cancer Foundation Finland; pBETTER4U_EU (Preventing obesity through Biologically and bEhaviorally Tailored inTERventions for you; project number: 101080117); CVDLink (EU grant nro. 101137278); and the Jane and Aatos Erkko Foundation. Pashupati P. Mishra (grant no. 349708) and Emma Raitoharju (grants 330809 and 338395) were supported by the Academy of Finland.
The DNA methylation measurement in the LURIC Study has been financially supported by the 7th Framework Programme RiskyCAD (grant agreement no. 305739) of the European Union and by the Competence Cluster of Nutrition and Cardiovascular Health (nutriCARD), which is funded by the German Federal Ministry of Education and Research (grant numbers 01EA1411A and 01EA1808A). LURIC has also received funding from the H2020 Programmes TO_AITION (grant agreement number 848146) and TIMELY (grant agreement number 101017424) of the European Union.
The KORA study was initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research (BMBF) and by the State of Bavaria. Data collection in the KORA study is carried out in cooperation with the University Hospital of Augsburg. Furthermore, the KORA research was supported within the Munich Center of Health Sciences (MC Health), Ludwig-Maximilians-Universität, as part of LMUinnovativ. The authors have no other relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
NFBC1966: We thank all cohort members and researchers who participated in the NFBC1966 study. We also wish to acknowledge the work of the NFBC project centre.
The NFBC1966 46-year follow-up received financial support from the University of Oulu (grant no. 24000692), Oulu University Hospital (grant no. 24301140) and the ERDF European Regional Development Fund (grant no. 539/2010 A31592). The researchers were supported by the European Union’s Horizon 2020 research and innovation programme (grant no. 874739 LongITools) and the Research Council of Finland (grant no. 356888).
The Bogalusa Heart Study has been financially supported by the National Institutes of Health (grants R01HD069587, R01AG016592, R01AG041200, P50HL015103 and R01HD032194). EWH was also supported by the Fulbright Finland Foundation.
Researchers in the current study have been supported by the Yrjö Jahnsson Foundation (grant no. 20217416), the Juho Vainio Foundation (grant number 202100335), the Päivikki and Sakari Sohlberg Foundation (grant number 220032) and the Tampere Tuberculosis Foundation (LK).
