Association of matrix metalloproteinase-10 levels and genetic variant rs17860955 with severe vascular complications in patients with type 1 diabetes: prospective cohort.
J M Zubiria, E Molina, E Toledo, L Forga, J Hermida
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引用次数: 0
Abstract
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.
期刊介绍：
Journal of Diabetes and Its Complications (JDC) is a journal for health care practitioners and researchers, that publishes original research about the pathogenesis, diagnosis and management of diabetes mellitus and its complications. JDC also publishes articles on physiological and molecular aspects of glucose homeostasis.
The primary purpose of JDC is to act as a source of information usable by diabetes practitioners and researchers to increase their knowledge about mechanisms of diabetes and complications development, and promote better management of people with diabetes who are at risk for those complications.
Manuscripts submitted to JDC can report any aspect of basic, translational or clinical research as well as epidemiology. Topics can range broadly from early prediabetes to late-stage complicated diabetes. Topics relevant to basic/translational reports include pancreatic islet dysfunction and insulin resistance, altered adipose tissue function in diabetes, altered neuronal control of glucose homeostasis and mechanisms of drug action. Topics relevant to diabetic complications include diabetic retinopathy, neuropathy and nephropathy; peripheral vascular disease and coronary heart disease; gastrointestinal disorders, renal failure and impotence; and hypertension and hyperlipidemia.
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