title: Matrix GLA protein gene polymorphisms: clinical correlates and cardiovascular mortality in chronic kidney disease patients.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Renal Division and Clinical Chemistry and Microbiology, S. Paolo Hospital, University of Milan, Italy. diego.brancaccio@tiscalinet.it
authors.forename: Diego
authors.initials: D
authors.lastname: Brancaccio
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Biondi
authors.forename: Maurizio
authors.initials: M
authors.lastname: Gallieni
authors.forename: Olivia
authors.initials: O
authors.lastname: Turri
authors.forename: Andrea
authors.initials: A
authors.lastname: Galassi
authors.forename: Federica
authors.initials: F
authors.lastname: Cecchini
authors.forename: Domenico
authors.initials: D
authors.lastname: Russo
authors.forename: Vittorio
authors.initials: V
authors.lastname: Andreucci
authors.forename: Mario
authors.initials: M
authors.lastname: Cozzolino
mesh_terms: D000368:Aged; D002114:Calcinosis / Q000209:etiology*; D002135:Calcium-Binding Proteins / Q000235:genetics*; D002318:Cardiovascular Diseases / Q000209:etiology*; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007676:Kidney Failure, Chronic / Q000150:complications / Q000235:genetics* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011446:Prospective Studies; D006435:Renal Dialysis; D000097568:Matrix Gla Protein
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein