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Promoter methylation status of the TIMP2 and ADAMTS4 genes and patellar tendinopathy

El Khoury, L. Y., Rickaby, R., Samiric, T. and Raleigh, S. M. (2018) Promoter methylation status of the TIMP2 and ADAMTS4 genes and patellar tendinopathy. Journal of Science and Medicine in Sport. 21(4), pp. 378-382. 1440-2440.

Item Type: Article
Abstract: Objectives Patellar tendinopathy (PT) is a debilitating and prevalent condition that tends to affect those who are physically active or engaged in jumping sports. Although tendinopathies are known to have a genetic basis, the role of DNA methylation as an epigenetic factor and risk determinant for human PT has never been described. We sought to determine whether differences existed between the methylation profiles of both the TIMP2 and ADAMTS4 gene promoter sequences in a cohort of males having undergone surgery for patellar tendinopathy compared to controls. Design Case-control epigenetic study using DNA from 10 males with PT and 10 males with healthy tendons. Methods We used PCR and targeted pyrosequencing to interrogate the methylation profiles of CpG sites upstream of both the TIMP2 (4 sites) and ADAMTS4 (6 sites) genes. We compared methylation differences between the two groups using t-tests. Results We report no significant (p > 0.05) methylation differences within the TIMP2 gene promoter between the PT group and controls across the 4 CpG sites investigated. In contrast, we detected a significant (p = 0.016) difference in the methylation status of 1 CpG site, approximately 3 kb upstream of the ADAMTS4 gene between the PT group and controls. Conclusions To our knowledge, this is the first study to investigate how DNA methylation impacts on the risk of human tendinopathy. Our data indicate that the methylation status of the ADAMTS4 gene is altered in patellar tendinopathy and we speculate on how this change might modify the patellar tendon extra-cellular matrix environment.
Uncontrolled Keywords: Epigenetics, Genetics, Sports injury, Tendinopathy, Tendon
Creators: El Khoury, Louis Y, Rickaby, Rebecca, Samiric, Tom and Raleigh, Stuart M
Faculties, Divisions and Institutes: Faculties > Faculty of Health & Society > Sports, Exercise & Life Sciences
Date: 1 April 2018
Date Type: Publication
Page Range: pp. 378-382
Journal or Publication Title: Journal of Science and Medicine in Sport
Volume: 21
Number: 4
Number of Pages: 5
Language: English
ISSN: 1440-2440
Status: Published / Disseminated
Refereed: Yes

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