Matrix GLA protein gene polymorphisms: clinical correlates and cardiovascular mortality in chronic kidney disease patients

Am J Nephrol. Nov-Dec 2005;25(6):548-52. doi: 10.1159/000088809. Epub 2005 Oct 5.

Abstract

Background: Increased vascular calcification plays an important role in the pathogenesis of cardiovascular events in chronic kidney disease (CKD) patients. It is the result of an active ossification process counteracted by 'protective' proteins, such as matrix GLA protein (MGP). Polymorphisms of MGP have been identified.

Methods: The aim of this study was to define the distribution of two MGP polymorphisms (-7, -138) in 99 hemodialysis (HD) patients, in 26 patients with CKD stage 3 and in 135 age- and sex-matched healthy controls. Patients were followed up for 12 months to record any cardiovascular deaths. The cause of death was determined by medical doctors, considering the medical history of each patient. The primers were designed with Primer Express software.

Results: MGP -138TT homozygotes were more frequent in the HD group versus controls (p = 0.0004). Additionally, the frequency of the T allele was significantly higher in the HD group (p = 0.0006). The frequency of the A allele of MGP-7 was significantly higher both in the HD group (p = 0.033) and in the CKD group (p = 0.0017) versus controls. MGP-7 GG homozygotes were significantly less common in the CKD group than in controls (p = 0.037). Combination -138TT -7AA was significantly more frequent in both CKD patients (p = 0.001) and in HD patients (p = 0.029) than in controls. Seventeen out of 99 HD patients experienced fatal cardiovascular events. Sixteen (94.1%) were -138TT homozygotes and either -7AA homozygotes or -7GA heterozygotes.

Conclusion: This study suggests that CKD and HD patients have a different distribution of MGP gene polymorphism as compared with the normal population. Altered MGP gene polymorphism may be a negative prognostic factor for the progression to end-stage renal disease and for cardiovascular events in CKD patients.

MeSH terms

  • Aged
  • Calcinosis / etiology*
  • Calcium-Binding Proteins / genetics*
  • Cardiovascular Diseases / etiology*
  • Case-Control Studies
  • Extracellular Matrix Proteins / genetics*
  • Female
  • Genotype
  • Humans
  • Kidney Failure, Chronic / complications
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Prospective Studies
  • Renal Dialysis

Substances

  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • matrix Gla protein