Genome-Wide Profiling of DNA from Cartilage Reveals Regions Differently Methylated in Osteoarthritis Patients

Guangju Zhai¹, Ming Liu², Yuhua Zhang¹, Patricia E. Harper¹, Erfan Aref-Eshghi², Glynn Martin³, Andrew Furey³, Roger Green¹, Guang Sun⁴ and Proton Rahman⁵, ¹Discipline of Genetics, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NF, Canada, ²Discipline of Genetics, Memorial University, St. John's, NF, Canada, ³Department of Surgery, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NF, Canada, ⁴Discipline of Medicine, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NF, Canada, ⁵Faculty of Medicine, Memorial University of Newfoundland, St. John's, NF, Canada

Meeting: 2014 ACR/ARHP Annual Meeting

Keywords: Epigenetics, genome and osteoarthritis

Session Information

Title: Genetics, Genomics and Proteomics II

Session Type: Abstract Submissions (ACR)

Background/Purpose: Osteoarthritis (OA) represents the most common form of arthritis and has substantial clinical and economic impact. Evidence supports that DNA methylation plays a significant role in OA. The aim of the study was to identify differentially methylated loci for OA using an epigenome-wide association approach.

Methods: Cartilage samples were collected from 14 patients who underwent total hip joint replacement due to primary OA and 16 hip fracture patients who do not have evidence of hip OA. DNA was extracted from the cartilage samples and methylation profiling was performed using the Illumina Infinium HumanMethylation 450k chip, which measures about 480,000 different CpG sites covering 96% of RefSeq genes. It provides comprehensive gene region coverage, targeting multiple sites including the promoter, 5’ UTR, 1^st exon, gene body and 3’ UTR. The methylation level at each CpG site was measured by β values varying from 0 (no methylation) to 1 (100% methylation).

Results: We found 18 individual CpG sites significantly associated with OA, with a mean difference in methylation level of >10% and a p value < 10^-4. Six of them were hypermethylated and 12 were hypomethylated in OA patients. Nine of them are located within genes and other 9 are intergenic. Two genes – COL8A1 and CDKN2C have been reported recently using the same approach as ours and the other 16 CpG sites are novel. ATG7 involving in autophagic pathway and CLCN7 causing osteopetrosis are novel promising candidates for OA.

Conclusion: We confirmed the recently reported association of COL8A1 and CDKN2C methylation with OA and identified 16 novel DNA methylation loci for OA, providing new insight into the pathogenesis of OA. Confirmation study with large sample size is underway.

Disclosure:

G. Zhai,
None;

M. Liu,
None;

Y. Zhang,
None;

P. E. Harper,
None;

E. Aref-Eshghi,
None;

G. Martin,
None;

A. Furey,
None;

R. Green,
None;

G. Sun,
None;

P. Rahman,
None.

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