Stefanos Roumeliotis1, Athanasios Roumeliotis1, Stylianos Panagoutsos1, Efstathia Giannakopoulou2, Nikolaos Papanas3, Vangelis G Manolopoulos2, Ploumis Passadakis1, Anna Tavridou4. 1. Department of Nephrology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. 2. Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. 3. Second Department of Internal Medicine, Diabetes Clinic, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. 4. Laboratory of Pharmacology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece. Electronic address: atavrid@med.duth.gr.
Abstract
AIMS: We sought to determine the predictive value of Matrix Gla Protein MGP T-138C polymorphism in relation to all-cause mortality, cardiovascular mortality and cardiovascular events in patients with diabetic nephropathy (DN). METHODS: MGP T-138C polymorphism was assessed in 40 diabetic patients without nephropathy and 118 patients at different stages of DN, including patients on hemodialysis. Measurement of carotid intima-media thickness (cIMT) was performed using real-time B-mode ultrasonography. Plasma levels of dephoshorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) were determined in a subgroup of 67 patients by ELISA. Mortality and cardiovascular events were assessed during a 7year follow-up. RESULTS: TT homozygotes for the MGP T-138C polymorphism had higher values of cIMT compared to combined TC and CC genotypes (P=0.006) whereas no association was observed between cIMT and dp-ucMGP levels. MGP T-138C polymorphism was a strong independent predictor of cIMT (P<0.0001), after adjustment for several well-known atherosclerosis risk factors. Patients with TT genotype presented a significantly higher all-cause and cardiovascular mortality risk compared to patients with TC and CC genotypes (P=0.01 and P=0.04 respectively), after adjustment for several traditional risk factors. CONCLUSIONS: MGP T-138C polymorphism is a strong and independent predictor of increased cIMT as well as all-cause and cardiovascular mortality in DN patients.
AIMS: We sought to determine the predictive value of Matrix Gla ProteinMGPT-138C polymorphism in relation to all-cause mortality, cardiovascular mortality and cardiovascular events in patients with diabetic nephropathy (DN). METHODS:MGPT-138C polymorphism was assessed in 40 diabeticpatients without nephropathy and 118 patients at different stages of DN, including patients on hemodialysis. Measurement of carotid intima-media thickness (cIMT) was performed using real-time B-mode ultrasonography. Plasma levels of dephoshorylated uncarboxylated Matrix Gla Protein (dp-ucMGP) were determined in a subgroup of 67 patients by ELISA. Mortality and cardiovascular events were assessed during a 7year follow-up. RESULTS: TT homozygotes for the MGPT-138C polymorphism had higher values of cIMT compared to combined TC and CC genotypes (P=0.006) whereas no association was observed between cIMT and dp-ucMGP levels. MGPT-138C polymorphism was a strong independent predictor of cIMT (P<0.0001), after adjustment for several well-known atherosclerosis risk factors. Patients with TT genotype presented a significantly higher all-cause and cardiovascular mortality risk compared to patients with TC and CC genotypes (P=0.01 and P=0.04 respectively), after adjustment for several traditional risk factors. CONCLUSIONS:MGPT-138C polymorphism is a strong and independent predictor of increased cIMT as well as all-cause and cardiovascular mortality in DN patients.