ACR Meeting Abstracts

ACR Meeting Abstracts

Abstract Number: 1893

Altered DNA Methylation Profiles In Individuals With Osteoarthritis

Kathryn A Bailey1, Daniel Rojas2, Nikhil Umesh1, Lisa Smeester1, Tristan De Buysscher3, Jordan B. Renner4, Joanne M. Jordan5 and Rebecca C. Fry1, 1Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 2School of Medicine, Curriculum in Toxicology, Univeristy of North Carolina at Chapel Hill, Chapel Hill, NC, 3Center for Bioinformatics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 4University of North Carolina Department of Radiology, Chapel Hill, NC, 5Thurston Arthritis Research Center, University of North Carolina, Chapel Hill, NC

Meeting: 2013 ACR/ARHP Annual Meeting

Keywords: ,

Session Information

Title: Genetics and Genomics of Rheumatic Disease II

Session Type: Abstract Submissions (ACR)

 

Background/Purpose: Major risk factors associated with osteoarthritis (OA) development include age, joint stress/injury, obesity, and genetic predisposition. In recent years, the role epigenetic processes that may be associated with OA have been of increasing interest both as factors implicated in disease development and as powerful diagnostic tools. Here, we set out to identify 5-methyl cytosine DNA methylation patterns associated with OA in participants of the Johnston County Osteoarthritis Project (JoCo OA), an ongoing study of North Carolinians of over 20 years.

Methods:   Genomic DNA was isolated from peripheral blood mononuclear cells (PMNCs) collected from 20 Caucasian, non-smoking, non-drinking women from the JoCo OA cohort. Methylated regions of PMNC 5-methyl cytosine DNA were isolated and amplified using the Methylated CpG Island Recovery Assay (MIRA) and subsequently hybridized to Affymetrix® Human Promoter 1.0R arrays. Controlling for known confounders (e.g. age and body mass index (BMI)), we compared the promoter DNA methylation profiles of >14,000 promoter regions of genes from women with knee OA (n=8) to women without knee OA  (n=12) using regression analysis. Differentially methylated genes were analyzed for associated biological functions, diseases, canonical pathways and molecular networks.

Results: A total of 68 genes were identified that had statistically significant differences in promoter DNA methylation levels in women with knee OA compared to women without knee OA. Most of these genes (n=61) showed hypomethylation in their promoter regions in individuals with knee OA. Analyses of associated biological functions, pathways and molecular networks revealed an enrichment of genes involved in varied cellular functions including tissue development, metabolism, and inflammation (Table). Several of these genes have prior associations with OA, namely connective tissue growth factor (CTGF), eyes absent homolog 4 (Drosophila)(EYA4), growth hormone receptor (GHR), and homeobox A2 (HOXA2).

  Conclusion: We identified genes in PBMCs with altered promoter DNA methylation levels associated with knee OA in this pilot study. Expanding these analyses to include more individuals from the JoCo OA cohort will determine if these DNA methylation profiles may serve as biomarkers of OA and/or provide insight into the role epigenetic alterations may play in OA development.  

Table. Most significant biological functions, canonical pathways and molecular networks associated with

differentially methylated genes in individuals with OA.

 

 

Biological functions

p-value

     Embryonic development

5.77 X 10-6—3.58 X 10-2

     Organismal development

5.77 X 10-6—3.58 X 10-2

     Tissue development

5.77 X 10-6—3.58 X 10-2

     Auditory and vestibular system development and function

1.63 X 10-5—3.31 X 10-2

     Organ morphology

1.63 X 10-6—3.58 X 10-2

Canonical pathways

p-value

     PRPP biosynthesis I

8.37 X 10-3

     Tetrapyrrole biosynthesis II

8.37 X 10-3

     Glycogen biosynthesis II

1.67 X 10-2

     NF-kB activation by viruses

1.67 X 10-2

     Heme biosynthesis II

1.82 X 10-2

Molecular network functions

p-value

     Hematological disease, nutritional disease, tissue  

     morphology

<10-40

     Cellular assembly and organization, cellular function and 

     maintenance, cell cycle

<10-32

      Cellular growth and proliferation, auditory and vestibular

     system development and function, embryonic development

<10-27

     Connective tissue disorders, developmental disorder,

     hereditary disorder

<10-12

     Molecular transport, RNA trafficking, RNA post-

     translational modification

<10-10

 

 

 

Disclosure:

K. A. Bailey,
None;

D. Rojas,
None;

N. Umesh,
None;

L. Smeester,
None;

T. De Buysscher,
None;

J. B. Renner,
None;

J. M. Jordan,

Trinity Partners, Inc. ,

5,

Osteoarthritis Research Society International,

6,

Chronic Osteoarthritis Management Initiative of US Bone and Joint Initiative,

6,

Samumed,

5,

Interleukin Genetics, Inc. ,

5,

Algynomics, Inc. ,

1;

R. C. Fry,
None.

« Back to 2013 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/altered-dna-methylation-profiles-in-individuals-with-osteoarthritis/