Last update:
   21-Jan-2019
 

Arch Hellen Med, 36(1), January-February 2019, 96-106

ORIGINAL PAPER

Association of matrix Gla Protein T-138C polymorphism with diabetic nephropathy and vascular calcification

S. Roumeliotis,1,3 A. Roumeliotis,1 S. Panagoutsos,1 M. Theodoridis,1 K. Kantartzi,1 A. Tavridou,2 P. Passadakis1
1Department of Nephrology, School of Medicine, Democritus University of Thrace, Alexandroupolis,
2Laboratory of Pharmacology, School of Medicine, Democritus University of Thrace, Alexandroupolis,
3Achilleion Nephrology Center, Thessaloniki, GreeceDepartment of Business Administration, Unit of Health and Welfare Management, Technological Educational Institute of Athens, Athens, Greece

OBJECTIVE To determine the plasma level of dp-uc matrix Gla protein (dpucMGP) in patients at all stages of diabetic nephropathy, including patients on hemodialysis, and to investigate its possible association with apoE, VKORC1-1639 G>A and MGP T-138C polymorphisms and carotid intima media thickness (cIMT).

METHOD Study was made of 40 patients with type 2 diabetes mellitus (T2DM) with normal renal function (control group) and 118 patients presenting all five stages of diabetic nephropathy (88 at stages 1–4 and 30 at stage 5 – hemodialysis). cIMT was measured using real-time B-mode ultrasonography (US), and apoE, VKORC1-1639 G>A and MGP T-138C polymorphisms were genotyped by PCR-RFLP. The plasma level of dp-ucMGP was determined in 67 of the patients by ELISA. The statistical significance of association was determined using the Kruskal-Wallis test.

RESULTS The plasma dp-ucMGP level was shown to be associated with both cIMT and progression of diabetic nephropathy (p<0.0001 and p=0.004, respectively). No association was found between ApoE and VKORC1-1639 G>A polymorphism and plasma level of dpucMGP. Although neither mean nor maximum cIMT showed significant difference among patients with VKORC1-1639 G >A and apoE polymorphisms, MGP TT homozygotes presented significantly higher mean/maximum cIMT than TC and CC genotypes (p=0.01 and p=0.05, respectively). The association between MGP T-138C and cIMT became even stronger when the genotypes were grouped (TT vs TC+CC genotypes, p=0.006 and p=0.022, respectively). An excess of TT homozygotes was observed in the hemodialysis group compared with the control and diabetic nephropathy groups 1–4 (p=0.012), which was more pronounced when TC and CC genotypes were grouped (p=0.002).

CONCLUSIONS The inactive form of MGP and its polymorphism appear to play a key role in both the pathogenesis of arterial calcification and the progression of diabetic nephropathy. These findings indicate that vascular calcification in diabetic nephropathy may have a genetic basis.

Key words: Carotid intima-media thickness, Diabetic nephropathy, Matrix Gla protein (MGP), Vascular calcification.

© Archives of Hellenic Medicine