Matrix metalloproteinase (MMP)-2 genetic variants modify the circulating MMP-2 levels in end-stage kidney disease.
BACKGROUND
Matrix metalloproteinases (MMPs) play important roles in the pathophysiology of renal diseases, and imbalanced MMP-2 and its endogenous inhibitor (the tissue inhibitor of metalloproteinases-2; TIMP-2) are implicated in the vascular alterations of end-stage kidney disease (ESKD) patients. We have examined whether MMP-2 gene polymorphisms and haplotypes modify MMP-2 and TIMP-2 levels in ESKD patients as well as the effects of hemodialysis on the concentrations of these biomarkers.


METHODS
We determined MMP-2 and TIMP-2 plasma levels by gelatin zymography and ELISA, respectively, in 98 ESKD patients and in 38 healthy controls. Genotypes for two relevant MMP-2 polymorphisms (C(-1306)T and C(-735)T in the promoter region) were determined by TaqMan(®) allele discrimination assay and real-time polymerase chain reaction. The software program PHASE 2.1 was used to estimate the haplotype frequencies.


RESULTS
We found increased plasma MMP-2 and TIMP-2 levels in ESKD patients compared to controls (p < 0.05), and hemodialysis decreased MMP-2 (but not TIMP-2) levels (p < 0.05). The T allele for the C(-735)T polymorphism and the C-T haplotype were associated with higher MMP-2 (but not TIMP-2) levels (p < 0.05), whereas the C(-1306)T had no effects. Hemodialysis decreased MMP-2 (but not TIMP-2) levels independently of MMP-2 genotypes or haplotypes (p < 0.05).


CONCLUSIONS
MMP-2 genotypes or haplotypes modify MMP-2 levels in ESKD patients, and may help to identify patients with increased MMP-2 activity in plasma. Hemodialysis reduces MMP-2 levels independently of MMP-2 genetic variants.
Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Brazil.
Bernardo P
BP
Marson
Riccardo
R
Lacchini
Vanessa
V
Belo
Samantha
S
Dickel
Bartira P
BP
da Costa
Carlos E
CE
Poli de Figueiredo
Jose E
JE
Tanus-Santos
D000328:Adult; D015415:Biomarkers; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000097:blood* / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D011110:Polymorphism, Genetic; D006435:Renal Dialysis; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood* / Q000378:metabolism
D015415:Biomarkers; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2; C522361:MMP2 protein, human; D020778:Matrix Metalloproteinase 2