Association of DNA Methylation Markers with C-reactive protein in African Americans Open Access
Chuang, Yu-Hsuan (2012)
Published
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
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