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

Bernardo P Marson1, Riccardo Lacchini, Vanessa Belo

  • 1Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.

Clinica Chimica Acta; International Journal of Clinical Chemistry
|September 27, 2012
PubMed
Abstract

Insights

Genetic variations in MMP-9 influence cardiovascular changes in end-stage kidney disease (ESKD) patients undergoing hemodialysis. Specific MMP-9 genotypes and haplotypes are linked to increased MMP-9 levels post-hemodialysis, suggesting potential therapeutic targets.

Area of Science:

  • Cardiovascular alterations in end-stage kidney disease (ESKD).
  • Role of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cardiovascular disease.
  • Impact of genetic polymorphisms on protein expression and function.

Background:

  • Cardiovascular complications are prevalent in ESKD patients.
  • Altered levels of MMPs and TIMPs contribute to cardiovascular alterations in ESKD.
  • Genetic variations in the MMP-9 gene can influence MMP-9 levels.

Purpose of the Study:

  • To investigate the impact of MMP-9 gene polymorphisms and haplotypes on plasma MMP-9 and TIMP-1 levels in ESKD patients undergoing hemodialysis.
  • To determine how hemodialysis affects MMP-9 and TIMP-1 levels in relation to MMP-9 genotypes and haplotypes.

Main Methods:

  • Study included 94 ESKD patients on hemodialysis.
  • Plasma MMP-9 and TIMP-1 levels were measured using ELISA before and after hemodialysis.
  • Genotyping for three MMP-9 polymorphisms (C(-1562)T, -90 (CA)(14-24), Q279R) and haplotype analysis were performed.

Main Results:

  • Hemodialysis significantly increased plasma MMP-9 and TIMP-1 levels.
  • The CC genotype for C(-1562)T and QQ genotype for Q279R were associated with increased MMP-9 and TIMP-1 levels post-hemodialysis.
  • The CLQ haplotype was linked to significant increases in MMP-9 levels and MMP-9/TIMP-1 ratios after hemodialysis.

Conclusions:

  • ESKD patients with the QQ genotype (Q279R) or CLQ haplotype exhibit greater MMP-9 level increases post-hemodialysis.
  • These specific genetic profiles may indicate higher cardiovascular risk in ESKD patients undergoing hemodialysis.
  • MMP inhibitors could be a potential therapeutic strategy for these patients.

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