Functional matrix metalloproteinase (MMP)-9 genetic variants modify the effects of hemodialysis on circulating MMP-9 levels.

Autor: Marson BP; Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil., Lacchini R, Belo V, Mattos SG, da Costa BP, Poli-de-Figueiredo CE, Tanus-Santos JE
Jazyk: angličtina
Zdroj: Clinica chimica acta; international journal of clinical chemistry [Clin Chim Acta] 2012 Dec 24; Vol. 414, pp. 46-51. Date of Electronic Publication: 2012 Aug 21.
DOI: 10.1016/j.cca.2012.08.014
Abstrakt: Background: Altered levels of matrix metalloproteinases (MMPs) and their inhibitors, the tissue inhibitors of metalloproteinases (TIMPs), are involved in cardiovascular alterations associated with end stage kidney disease (ESKD). Genetic polymorphisms in MMP-9 gene affect MMP-9 levels. We examined how MMP-9 polymorphisms and haplotypes affect the changes in plasma MMP-9 and TIMP-1 levels found in patients with ESKD undergoing hemodialysis.
Methods: We studied 94 ESKD patients undergoing hemodialysis for at least 3 months. MMP-9 and TIMP-1 were measured by ELISA in plasma from blood samples collected before and after a session of hemodialysis. Genotypes for three MMP-9 polymorphisms (C(-1562)T, rs3918242; -90 (CA)(14-24), rs2234681; and Q279R, rs17576) were determined by Taqman® Allele Discrimination Assay and real-time polymerase chain reaction. Haplotype frequencies were determined with the software program PHASE 2.1.
Results: Hemodialysis increased MMP-9 and TIMP-1 levels (P<0.05). Genotypes had no effects on baseline MMP-9 and TIMP-1 levels (P>0.05). Hemodialysis increased MMP-9 and TIMP-1 levels in subjects with the CC (but not CT or TT) genotype for the C(-1562)T polymorphism (P<0.05), and increased MMP-9 levels in subjects with the QQ (but not QR or RR) genotype for the Q279R polymorphism (P<0.05), whereas the CA(n)(14-24) polymorphism had no major effects. While MMP-9 haplotypes had no effects on baseline MMP-9 levels (P>0.05), hemodialysis increased MMP-9 levels and MMP-9/TIMP-1 ratios in subjects carrying the CLQ haplotype (P=0.0012 and P=0.0045, respectively).
Conclusion: ESKD patients with the QQ genotype for the Q279R polymorphism or with the CLQ haplotype are exposed to more severe increases in MMP-9 levels after hemodialysis. Such patients may benefit from the use of MMP inhibitors.
(Copyright © 2012 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: