2026-08-29T14:17:46Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/238432025-12-18T12:57:00Zcom_20.500.12105_2052com_20.500.12105_2051col_20.500.12105_19608

00925njm 22002777a 4500 dc Lieberman-Cribbin, Wil author Domingo-Relloso, Arce author Glabonjat, Ronald A author Schilling, Kathrin author Cole, Shelley A author O'Leary, Marcia author Best, Lyle G author Zhang, Ying author Fretts, Amanda M author Umans, Jason G author Goessler, Walter author Navas-Acien, Ana author Tellez-Plaza, Maria author Kupsco, Allison author Lieberman-Cribbin, Wil author Domingo-Relloso, Arce author Glabonjat, Ronald A author Schilling, Kathrin author Cole, Shelley A author O'Leary, Marcia author Best, Lyle G author Zhang, Ying author Fretts, Amanda M author Umans, Jason G author Goessler, Walter author Navas-Acien, Ana author Kupsco, Allison author 2024-09 Background: Selenium (Se) is an essential nutrient linked to adverse health endpoints at low and high levels. The mechanisms behind these relationships remain unclear and there is a need to further understand the epigenetic impacts of Se and their relationship to disease. We investigated the association between urinary Se levels and DNA methylation (DNAm) in the Strong Heart Study (SHS), a prospective study of cardiovascular disease (CVD) among American Indians adults. Methods: Selenium concentrations were measured in urine (collected in 1989-1991) using inductively coupled plasma mass spectrometry among 1,357 participants free of CVD and diabetes. DNAm in whole blood was measured cross-sectionally using the Illumina MethylationEPIC BeadChip (850 K) Array. We used epigenome-wide robust linear regressions and elastic net to identify differentially methylated cytosine-guanine dinucleotide (CpG) sites associated with urinary Se levels. Results: The mean (standard deviation) urinary Se concentration was 51.8 (25.1) μg/g creatinine. Across 788,368 CpG sites, five differentially methylated positions (DMP) (hypermethylated: cg00163554, cg18212762, cg11270656, and hypomethylated: cg25194720, cg00886293) were significantly associated with Se in linear regressions after accounting for multiple comparisons (false discovery rate p-value: 0.10). The top hypermethylated DMP (cg00163554) was annotated to the Disco Interacting Protein 2 Homolog C (DIP2C) gene, which relates to transcription factor binding. Elastic net models selected 425 hypo- and hyper-methylated DMPs associated with urinary Se, including three sites (cg00163554 [DIP2C], cg18212762 [MAP4K2], cg11270656 [GPIHBP1]) identified in linear regressions. Conclusions: Urinary Se was associated with minimal changes in DNAm in adults from American Indian communities across the Southwest and the Great Plains in the United States, suggesting that other mechanisms may be driving health impacts. Future analyses should explore other mechanistic biomarkers in human populations, determine these relationships prospectively, and investigate the potential role of differentially methylated sites with disease endpoints. Environ Int. 2024 Sep:191:108955 10.1016/j.envint.2024.108955 1873-6750 0160-4120 Environment international. 39154409 https://hdl.handle.net/20.500.12105/23843 American Indian populations DNA methylation Epigenetics Selenium Strong Heart Study An epigenome-wide study of selenium status and DNA methylation in the Strong Heart Study