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

Louis Y El Khoury, Rebecca Rickaby, Tom Samiric, Stuart M Raleigh

Research output: Contribution to journalArticle

5 Citations (Scopus)
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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 3kb 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.

Original languageEnglish
Pages (from-to)378-382
Number of pages5
JournalJournal of Science and Medicine in Sport
Volume21
Issue number4
Early online date1 Sep 2017
DOIs
Publication statusPublished - Apr 2018
Externally publishedYes

Fingerprint

Tendinopathy
Methylation
Genes
DNA Methylation
Epigenomics
Patellar Ligament
Control Groups
Tendons
Sports
Case-Control Studies
Polymerase Chain Reaction
DNA

Bibliographical note

NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Science and Medicine in Sport. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Science and Medicine in Sport, [21, 4, (2018)] DOI: 10.1016/j.jsams.2017.08.016

© 2018, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

  • ADAMTS4 Protein
  • Case-Control Studies
  • CpG Islands
  • DNA Methylation
  • Epigenesis, Genetic
  • Humans
  • Male
  • Patellar Ligament
  • Promoter Regions, Genetic
  • Tendinopathy
  • Tissue Inhibitor of Metalloproteinase-2
  • Journal Article

Cite this

Promoter methylation status of the TIMP2 and ADAMTS4 genes and patellar tendinopathy. / El Khoury, Louis Y; Rickaby, Rebecca; Samiric, Tom; Raleigh, Stuart M.

In: Journal of Science and Medicine in Sport, Vol. 21, No. 4, 04.2018, p. 378-382.

Research output: Contribution to journalArticle

El Khoury, Louis Y ; Rickaby, Rebecca ; Samiric, Tom ; Raleigh, Stuart M. / Promoter methylation status of the TIMP2 and ADAMTS4 genes and patellar tendinopathy. In: Journal of Science and Medicine in Sport. 2018 ; Vol. 21, No. 4. pp. 378-382.
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N1 - NOTICE: this is the author’s version of a work that was accepted for publication in Journal of Science and Medicine in Sport. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of Science and Medicine in Sport, [21, 4, (2018)] DOI: 10.1016/j.jsams.2017.08.016 © 2018, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/

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N2 - 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 3kb 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.

AB - 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 3kb 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.

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