Repositorio
Institucional

Domingo-Relloso, Arce

Gribble, Matthew O.

Riffo-Campos, Angela L.

Haack, Karin

Cole, Shelley A.

Tellez-Plaza, Maria

Umans, Jason G.

Fretts, Amanda M.

Zhang, Ying

Fallin, M. Daniele

Navas-Acien, Ana

Everson, Todd M.

Epigenetics of type 2 diabetes and diabetes-related outcomes in the Strong Heart Study

BMC

CLINICAL EPIGENETICS

en

Background: The prevalence of type 2 diabetes has dramatically increased in the past years. Increasing evidence supports that blood DNA methylation, the best studied epigenetic mark, is related to diabetes risk. Few prospective studies, however, are available. We studied the association of blood DNA methylation with diabetes in the Strong Heart Study. We used limma, Iterative Sure Independence Screening and Cox regression to study the association of blood DNA methylation with fasting glucose, HOMA-IR and incident type 2 diabetes among 1312 American Indians from the Strong Heart Study. DNA methylation was measured using Illumina's MethylationEPIC beadchip. We also assessed the biological relevance of our findings using bioinformatics analyses. Results: Among the 358 differentially methylated positions (DMPs) that were cross-sectionally associated either with fasting glucose or HOMA-IR, 49 were prospectively associated with incident type 2 diabetes, although no DMPs remained significant after multiple comparisons correction. Multiple of the top DMPs were annotated to genes with relevant functions for diabetes including SREBF1, associated with obesity, type 2 diabetes and insulin sensitivity, ABCG1, involved in cholesterol and phospholipids transport, and HDAC1, of the HDAC family. (HDAC inhibitors have been proposed as an emerging treatment for diabetes and its complications.) Conclusions: Our results suggest that differences in peripheral blood DNA methylation are related to cross-sectional markers of glucose metabolism and insulin activity. While some of these DMPs were modestly associated with prospective incident type 2 diabetes, they did not survive multiple testing. Common DMPs with diabetes epigenome-wide association studies from other populations suggest a partially common epigenomic signature of glucose and insulin activity.

2022

artículo original

10.1186/s13148-022-01392-7

PDF

Epigenetics

Type 2 diabetes

DNA methylation

American Indians

Oncología

Genética y herencia

Epigenética

Diabetes tipo 2

metilación del ADN

indios americanos

artículo original

versión publicada

CC BY 4.0

CC BY 4.0

acceso abierto

acceso abierto

WOS:000900144600002

1868-7075

verde# dorado

Oncología

Genética y herencia