Matrix Gla protein T-138C polymorphism is associated with carotid intima media thickness and predicts mortality in patients with diabetic nephropathy

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 7 year 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 clIVTT 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. (C) 2017 Elsevier Inc. All rights reserved.