Methylation changes in the peripheral blood of Filipinos with type 2 diabetes suggest spurious transcription initiation at TXNIP.
| Title: | Methylation changes in the peripheral blood of Filipinos with type 2 diabetes suggest spurious transcription initiation at TXNIP. |
|---|---|
| Authors: | Albao DS; Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Ermita, Manila 1000, Philippines.; National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman, Diliman, Quezon City 1101, Philippines.; Philippine Genome Center, University of the Philippines System, Diliman, Quezon City 1101, Philippines.; Cutiongco-de la Paz EM; Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Ermita, Manila 1000, Philippines.; Philippine Genome Center, University of the Philippines System, Diliman, Quezon City 1101, Philippines.; Mercado ME; Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Ermita, Manila 1000, Philippines.; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94143, USA.; Lirio A; Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Ermita, Manila 1000, Philippines.; Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA 94143, USA.; Mariano M; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA.; Kim S; Division of Endocrinology, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.; Yangco A; Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Ermita, Manila 1000, Philippines.; Melegrito J; Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Ermita, Manila 1000, Philippines.; Wad-Asen K; Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Ermita, Manila 1000, Philippines.; Gauran II; School of Statistics, University of the Philippines Diliman, Diliman, Quezon City 1101, Philippines.; Francisco MA; Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Ermita, Manila 1000, Philippines.; National Institute of Molecular Biology and Biotechnology, University of the Philippines Diliman, Diliman, Quezon City 1101, Philippines.; Philippine Genome Center, University of the Philippines System, Diliman, Quezon City 1101, Philippines.; Santos-Acuin C; International Rice Research Institute, Los Baños 4031, Laguna, Philippines.; David-Padilla C; Institute of Human Genetics, National Institutes of Health, University of the Philippines Manila, Ermita, Manila 1000, Philippines.; Murphy EJ; Division of Endocrinology, Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.; Paz-Pacheco E; Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, University of the Philippines Manila, Ermita, Manila 1000, Philippines.; Seielstad M; Institute for Human Genetics, University of California San Francisco, San Francisco, CA 94143, USA. |
| Source: | Human molecular genetics [Hum Mol Genet] 2019 Dec 15; Vol. 28 (24), pp. 4208-4218. |
| Publication Type: | Journal Article; Research Support, Non-U.S. Gov't |
| Language: | English |
| Journal Info: | Publisher: IRL Press at Oxford University Press Country of Publication: England NLM ID: 9208958 Publication Model: Print Cited Medium: Internet ISSN: 1460-2083 (Electronic) Linking ISSN: 09646906 NLM ISO Abbreviation: Hum Mol Genet Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: Oxford, England ; New York : IRL Press at Oxford University Press, c1992- |
| MeSH Terms: | Carrier Proteins/*genetics ; Diabetes Mellitus, Type 2/*blood ; Diabetes Mellitus, Type 2/*genetics; Carrier Proteins/blood ; Carrier Proteins/metabolism ; Diabetes Mellitus, Type 2/metabolism ; Genome-Wide Association Study/methods ; Adult ; Asian ; DNA Methylation ; Epigenesis, Genetic ; Female ; Humans ; Male ; Middle Aged |
| 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.; (© The Author(s) 2019. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.) |
| Substance Nomenclature: | 0 (Carrier Proteins); 0 (TXNIP protein, human) |
| Entry Date(s): | Date Created: 20191107 Date Completed: 20200623 Latest Revision: 20221207 |
| Update Code: | 20260130 |
| DOI: | 10.1093/hmg/ddz262 |
| PMID: | 31691802 |
| Database: | MEDLINE |
Journal Article; Research Support, Non-U.S. Gov't