Association of matrix metalloproteinase-10 levels and genetic variant rs17860955 with severe vascular complications in patients with type 1 diabetes: prospective cohort

AIMS/HYPOTHESIS: The role of matrix metalloproteinase-10 (MMP-10) in the development of severe complications in patients with type 1 diabetes is not fully understood. The hypothesis is that elevated MMP-10 levels are associated with increased risk of severe complications and that genetic variants leading to reduced or non-functional MMP-10 may confer cardiovascular protection. METHODS: 195 patients with type 1 diabetes were recruited between 2007 and 2010. Serum MMP-10 concentrations were measured at baseline, and participants were prospectively followed until 2020. The association between baseline MMP-10 levels and a composite endpoint of severe complications of diabetes was analysed. In addition, genetic analysis of the MMP10 gene was performed to identify mutations that can result in a non-functional MMP-10 and lead to cardiovascular protection. RESULTS: Participants in the highest quartile of MMP-10 levels had a threefold higher risk of reaching the composite endpoint compared to those in the lowest quartile (p = 0.038). Moreover, there was a common polymorphism rs17860955 (minor allele frequency: 12 %) that lead to a non-functional MMP-10. These variant carriers showed significantly lower MMP-10 concentration (457.8 ± 309.9 pg/ml vs 942.1 ± 519.6 pg/ml; p < 0.0001) and non-significantly lower composite endpoint events. CONCLUSIONS: Low MMP-10 concentration is associated to protection against severe vascular complications in patients with type 1 diabetes. There is a frequent polymorphism (rs17860955) that leads to lower MMP-10 levels and may offer a degree of cardiovascular protection.