title: Influence of ACE I/D Polymorphism on Circulating Levels of Plasminogen Activator Inhibitor 1, D-Dimer, Ultrasensitive C-Reactive Protein and Transforming Growth Factor β1 in Patients Undergoing Hemodialysis.
abstract: BACKGROUND
  There is substantial evidence that chronic renal and cardiovascular diseases are associated with coagulation disorders, endothelial dysfunction, inflammation and fibrosis. Angiotensin-Converting Enzyme Insertion/Deletion polymorphism (ACE I/D polymorphism) has also be linked to cardiovascular diseases. Therefore, this study aimed to compare plasma levels of ultrassensible C-reactive protein (usCRP), PAI-1, D-dimer and TGF-β1 in patients undergoing HD with different ACE I/D polymorphisms.
  
  
  METHODS
  The study was performed in 138 patients at ESRD under hemodialysis therapy for more than six months. The patients were divided into three groups according to the genotype. Genomic DNA was extracted from blood cells (leukocytes). ACE I/D polymorphism was investigated by single polymerase chain reaction (PCR). Plasma levels of D-dimer, PAI-1 and TGF-β1 were measured by enzyme-linked immunosorbent assay (ELISA), and the determination of plasma levels of usCRP was performed by immunonephelometry. Data were analyzed by the software SigmaStat 2.03.
  
  
  RESULTS
  Clinical characteristics were similar in patients with these three ACE I/D polymorphisms, except for interdialytic weight gain. I allele could be associated with higher interdialytic weight gain (P = 0.017). Patients genotyped as DD and as ID had significantly higher levels of PAI-1 than those with II genotype. Other laboratory parameters did not significantly differ among the three subgroups (P = 0.033). Despite not reaching statistical significance, plasma levels of usCRP were higher in patients carrying the D allele.
  
  
  CONCLUSIONS
  ACE I/D polymorphisms could be associated with changes in the regulation of sodium, fibrinolytic system, and possibly, inflammation. Our data showed that high levels of PAI-1 are detected when D allele is present, whereas greater interdialytic gain is associated with the presence of I allele. However, further studies with different experimental designs are necessary to elucidate the mechanisms involved in these associations.
authors.affiliation: Campus Centro Oeste Dona Lindu, Universidade Federal de São João del-Rei, Divinópolis/MG - Brazil.
authors.forename: Sara Santos
authors.initials: SS
authors.lastname: de Carvalho
authors.affiliation: Department of Pediatrics, Interdisciplinary Laboratory of Medical Investigation, Faculty of Medicine - Universidade Federal de Minas Gerais, Belo Horizonte/MG - Brazil.
authors.forename: Ana Cristina
authors.initials: AC
authors.lastname: Simões e Silva
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy - Universidade Federal de Minas Gerais, Belo Horizonte/MG - Brazil.
authors.forename: Adriano de Paula
authors.initials: Ade P
authors.lastname: Sabino
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy - Universidade Federal de Minas Gerais, Belo Horizonte/MG - Brazil.
authors.forename: Fernanda Cristina Gontijo
authors.initials: FC
authors.lastname: Evangelista
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy - Universidade Federal de Minas Gerais, Belo Horizonte/MG - Brazil.
authors.forename: Karina Braga
authors.initials: KB
authors.lastname: Gomes
authors.affiliation: Department of Clinical and Toxicological Analysis, Faculty of Pharmacy - Universidade Federal de Minas Gerais, Belo Horizonte/MG - Brazil.
authors.forename: Luci Maria SantAna
authors.initials: LM
authors.lastname: Dusse
authors.affiliation: Campus Centro Oeste Dona Lindu, Universidade Federal de São João del-Rei, Divinópolis/MG - Brazil.
authors.forename: Danyelle Romana Alves
authors.initials: DR
authors.lastname: Rios
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006487:Hemostasis; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics*; D007249:Inflammation / Q000235:genetics; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*; D011110:Polymorphism, Genetic; D006435:Renal Dialysis; D053773:Transforming Growth Factor beta1 / Q000097:blood*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; D053773:Transforming Growth Factor beta1; C036309:fibrin fragment D; D002097:C-Reactive Protein; C488034:ACE protein, human; D007703:Peptidyl-Dipeptidase A