Faculty of Health and Society, University of Northampton, UK.
Faculty of Science, School of Pharmacy, University of Nottingham, UK.
J Sports Sci Med. 2019 Feb 11;18(1):155-159. eCollection 2019 Mar.
Patellar tendinopathy (PT) is a debilitating condition that often affects those who are physically active. Gene variation is known to contribute to human tendinopathy but the role of DNA methylation, as an epigenetic factor, has only recently been discovered. Using a case-control approach, we sought to determine whether differences existed between the methylation status of the gene promoter in patellar tendinopathy compared to healthy tendon. We used PCR and pyrosequencing to interrogate the methylation profiles of 4 CpG sites (areas of the genome rich in C/G nucleotides) upstream of the gene in DNA from males with PT (n = 10) and those with healthy tendon (n = 10). We also conducted a correlation analysis to establish whether age influenced methylation in the PT patients and controls. We found a significant (p = 0.045) difference in the methylation status of a single CpG site 65 base pairs (bp) upstream of the promoter between the PT group and controls. There were no other differences in the extent of promoter methylation between the two groups. Interestingly, we also found that in controls the degree of methylation at a second CpG site, 55 bp upstream of the first exon, tentatively correlated (r = 0.77, p = 0.009) with age. However, the correlation did not reach significance when a potential outlier was removed. This is the first study to show an epigenetic alteration to a member of the gene family in human patellar tendinopathy. The data add to our understanding of how epigenetics should be considered when developing appropriate risk models.
髌腱病（PT）是一种使人虚弱的疾病，通常影响那些积极活动的人。基因变异被认为是导致人类腱病的原因之一，但 DNA 甲基化作为一种表观遗传因素的作用直到最近才被发现。我们采用病例对照的方法，试图确定髌腱病患者与健康肌腱之间基因启动子的甲基化状态是否存在差异。我们使用 PCR 和焦磷酸测序技术检测了来自患有 PT（n=10）和健康肌腱（n=10）男性的 DNA 中基因启动子上游的 4 个 CpG 位点（富含 C/G 核苷酸的基因组区域）的甲基化谱。我们还进行了相关性分析，以确定年龄是否影响 PT 患者和对照组的甲基化。我们发现，在基因启动子上游 65 个碱基对（bp）处的单个 CpG 位点的甲基化状态在 PT 组和对照组之间存在显著差异（p=0.045）。两组之间基因启动子甲基化程度没有其他差异。有趣的是，我们还发现，在对照组中，第二个 CpG 位点的甲基化程度（第一个外显子上游 55bp）与年龄有初步相关性（r=0.77，p=0.009）。然而，当去除一个潜在的离群值时，相关性并没有达到显著水平。这是第一项表明人类髌腱病中基因家族成员存在表观遗传改变的研究。该数据增加了我们对在开发合适的风险模型时应如何考虑表观遗传学的理解。
