Epigenetic Status of The Human MMP11 Gene Promoter is Altered in Patellar Tendinopathy.

Abstract

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 MMP11 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 MMP11 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 MMP11 promoter between the PT group and controls. There were no other differences in the extent of MMP11 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 MMP gene family in human patellar tendinopathy. The data add to our understanding of how epigenetics should be considered when developing appropriate risk models.