Methylation changes in the peripheral blood of Filipinos with type 2 diabetes suggest spurious transcription initiation at TXNIP

Dominic S. Albao, Eva Maria Cutiongco-De La Paz*, Maria Elizabeth Mercado, Alvin Lirio, Margarette Mariano, Sarah Kim, Ariane Yangco, Jodelyn Melegrito, Kate Wad-Asen, Iris Ivy Gauran, Marie Angeline Francisco, Cecilia Santos-Acuin, Carmencita David-Padilla, Elizabeth J. Murphy, Elizabeth Paz-Pacheco, Mark Seielstad

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

While much work has been done in associating differentially methylated positions (DMPs) to type 2 diabetes (T2D) across different populations, not much attention has been placed on identifying its possible functional consequences. We explored methylation changes in the peripheral blood of Filipinos with T2D and identified 177 associated DMPs. Most of these DMPs were associated with genes involved in metabolism, inflammation and the cell cycle. Three of these DMPs map to the TXNIP gene body, replicating previous findings from epigenome-wide association studies (EWAS) of T2D. The TXNIP downmethylation coincided with increased transcription at the 3′ UTR, H3K36me3 histone markings and Sp1 binding, suggesting spurious transcription initiation at the TXNIP 3′ UTR as a functional consequence of T2D methylation changes. We also explored potential epigenetic determinants to increased incidence of T2D in Filipino immigrants in the USA and found three DMPs associated with the interaction of T2D and immigration. Two of these DMPs were located near MAP2K7 and PRMT1, which may point towards dysregulated stress response and inflammation as a contributing factor to T2D among Filipino immigrants.

Original languageEnglish (US)
Pages (from-to)4208-4218
Number of pages11
JournalHuman Molecular Genetics
Volume28
Issue number24
DOIs
StatePublished - Dec 15 2019

Bibliographical note

Funding Information:
Commission on Higher Education-Philippine-California Advanced Research Institutes (CHED-PCARI IHTM 2015-03).

Publisher Copyright:
© 2019 The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

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