THU0017 Dna methylation of regulatory sites of hand osteoarthritis susceptibility genes in finnish women. (12th June 2018)

• Record Type: Journal Article
• Authors: Hämäläinen, S.; Solovieva, S.; Vehmas, T.; Hirvonen, A.; Leino-Arjas, P.
• Is Part Of: Annals of the rheumatic diseases. Volume 77(2018)Supplement 2
• Page Start: 237
• Page End: 237
• Publication Date: 2018-06-12
• Subjects: Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2018-eular.1067
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Background: Despite the hard effort in OA genetic studies only a small part of the estimated effect has been found so far and thus the focus has been changing from genetic to epigenetic studies. The most widely studied epigenetic control mechanism is DNA methylation. There are only few studies on hand OA concerning DNA methylation but their results are promising. Objectives: Our aim was to study methylation of the regulatory sites of our previously found hand OA susceptibility genes and to replicate some previously reported methylation sites associated with hand OA, in our Finnish women hand OA material. Methods: The study design was cross-sectional. Bilateral hand radiographs of 542 occupationally active Finnish female dentists and teachers aged 45 to 63 and classified them according to the presence of OA by using reference images. Radiographic hand OA at least mild, in at least three joints (ROA2_3), and radiographic findings summary score (OASUM) were used to define hand OA status. The methylation percentages were determined by bi-sulfite converted DNA pyrosequencing with commercial CpG Assays. Statistical analyses were performed using hierarchical multiple linear regression. Results: Of the studied methylation sites the COL2A1_1 methylation site was associated with ROA2_3 (p=0.04). Also ALDH1A2_01 methylation site was associated with OASUM (p=0.02). When the data was stratified by occupation the association was only significant, and stronger, in teachers but not in dentists ( COL2A1_1 p=0.02 vs. p=0.36 for ROA2_3, and ALDH1A2_1 p=0.01 vs. p=0.36 for OASUM, respectively). The studied methylation sites in TGFB1, RRP9 and TRAPP5 genes had methylation percentages under the detection limit and they were excluded from the analysis. Conclusions: Our results lend further support to COL2A1 and ALDH1A2 being hand OA susceptibility genes at the epigenetic level. Acknowledgements: The study was financially supported by a grant from the Finnish Work Environment Fund (113369). Disclosure of Interest: None declared