DNA Methylation Association with Chronic Inflammation: A Twin Study Open Access

Yin, Jie (2016)

Permanent URL: https://etd.library.emory.edu/concern/etds/1z40kt08g?locale=en
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Abstract

Inflammation plays a very important role in chronic diseases including cardiovascular disease (CVD). DNA methylation (DNAm) is a basic mechanism regulating gene expression and can be affected and modified by chronic inflammation. To understand the influence of chronic inflammation on DNA methylation, we conducted an epigenome-wide association study using a twin-specific model to investigate the epigenetic associations with eight CVD-associated inflammatory biomarkers, by measuring 409,968 DNAm sites of peripheral blood leukocytes from 217 Caucasian male twins. By conducting linear mixed models, no methylome-wide significant association was found corrected for multiple testing across all the eight inflammatory biomarkers, adjusted for age, body max index, smoking status, and cell type proportions of peripheral leukocytes. However, 45 DNAm cites reached a threshold for suggestive significance (p-value <10-5), among which 66.7% were hypermethylated with lower levels of inflammatory biomarkers. The most Gene Ontology terms enriched among these suggestive genes were "intracellular" and "binding". In addition, four DNAm cites were associated with at least two inflammatory biomarkers. DNAm sites cg03359731 (OCIAD1) and cg14557787 (AP2A1) were related to the serum levels of both CRP and IL-6; cg17598713 (RGL2) was associated with ICAM-1 and VCAM-1; cg00459119 (SNX29) was associated with ICAM-1 and P-selectin. Although further replication and validation are needed, our results may provide evidence to investigate the mechanism of the process of inflammation affects CVDs through epigenetic modifications.

Table of Contents

LITERATURE REVIEW.......................1

METHODS.................................6

RESULTS................................11

DISCUSSION.............................13

REFERENCES.............................17

TABLES.................................23

FIGURES................................28

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