Association of DNA Methylation Markers with C-reactive protein in African Americans Open Access

Abstract

C-reactive protein (CRP), a nonspecific acute-phase protein in response to inflammatory reaction, has been shown highly correlated with increased risks for cardiovascular disease in epidemiological studies. DNA methylation is an epigenetic mechanism regulating gene expression. Investigating the association of DNA methylation sites with serum CRP levels may improve understanding of the etiology of inflammation and cardiovascular disease. A cross sectional study was used to determine the association between serum levels of CRP and gene-specific DNA methylation among African Americans. The study population consisted of 966 African Americans from 492 hypertensive sibships of the Genetic Epidemiology Network of Arteriopathy (GENOA) study. The GENOA data included demographic information and biomarkers of cardiovascular disease. DNA methylation data of 27,578 DNA methylation sites were obtained from Illumina Infinium HumanMethylation27 BeadChip using DNA samples extracted from peripheral blood cell. Linear mixed models were applied to identify gene-specific DNA methylation sites associated with the serum levels of CRP, and adjust for relatedness and potential confounders, including age, gender, BMI, and smoking status. Two hundred and fifty seven (1.12%) DNA methylation sites are significantly associated with serum level of CRP correcting for 22,927 tests using Bonferroni method. Moreover, among 257 significant DNA methylation sites, 80.5% (n=207) of the significant DNA methylation sites were hypomethylated with higher CRP levels. Analysis of the gene ontology showed that the CRP-associated DNA methylation sites were enriched by genes involved in inflammation and immune response. (Fisher Exact p-value= 4.50x10^-4 and 2.10x10^-15 respectively)

Table of Contents

Table of Contents

INTRODUCTION...1
LITERATURE REVIEW...3
METHODS...9
RESULTS...13
DISCUSSION...16
REFERENCES...19
TABLES...27

About this Master's Thesis

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School	Rollins School of Public Health
Department	Epidemiology
Degree	MPH
Submission	Master's Thesis
Language	English
Research Field	Biology, Genetics Biology, Bioinformatics Health Sciences, Epidemiology
Keyword	DNA methylation CVD CRP inflammation African American GENOA cardiovascular disease immune response C reactive protein CRP-associated DNA methylation
Committee Chair / Thesis Advisor	Sun, Yan, Emory University
Partnering Agencies	University, college or educational institution (other than Emory)

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