title: MMP-1 and -3 haplotype is associated with congenital anomalies of the kidney and urinary tract.
abstract: BACKGROUND
  Congenital anomalies of the kidney and urinary tract (CAKUT) are a common cause of progressive chronic kidney disease that may lead to end-stage renal disease and renal replacement therapy in childhood. Altered expression or activity of matrix metalloproteinases (MMPs) have been found in CAKUT. The MMP-1, -3, and -8 polymorphisms studied here are located in the gene promoters and alter expression. Our aim was to investigate associations of MMP polymorphisms, solely and in haplotypes, with CAKUT in children.
  
  
  METHODS
  A case-control study with 101 pediatric patients and 281 controls was performed. The MMP-1 (-1607 1G/2G), -3 (5A/6A), and -8 (-799 C/T) genotypes were determined by PCR-restriction fragment length polymorphism.
  
  
  RESULTS
  We found statistically significant associations of MMP-3 5A/6A polymorphism (p < 0.0001) and 1G-(1607)-6A haplotype, with no preferences for MMP-8 -799C or T alleles, with CAKUT (OR = 2.93, 95 % CI 1.43-5.98, adjusted for gender, p = 0.003) and with obstructive uropathies in a subgroup of patients (OR = 4.57, 95 % CI 2.74-7.61, adjusted for gender, p < 0.0001).
  
  
  CONCLUSIONS
  MMP-3 genotypes and MMP-3 and -1 haplotypes encompassing either MMP-8 -799C or T alleles were associated with CAKUT and obstructive uropathies in pediatric patients. Still, functional and association studies are needed to elucidate evident roles of MMPs in CAKUT.
authors.affiliation: Institute of Nuclear Sciences Vinca, Laboratory for Radiobiology and Molecular Genetics, University of Belgrade, Belgrade, Serbia.
authors.forename: Tamara
authors.initials: T
authors.lastname: Djuric
authors.forename: Maja
authors.initials: M
authors.lastname: Zivkovic
authors.forename: Biljana
authors.initials: B
authors.lastname: Milosevic
authors.forename: Magdalena
authors.initials: M
authors.lastname: Andjelevski
authors.forename: Mirjana
authors.initials: M
authors.lastname: Cvetkovic
authors.forename: Mirjana
authors.initials: M
authors.lastname: Kostic
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Stankovic
mesh_terms: D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007223:Infant; D007668:Kidney / Q000002:abnormalities*; D007674:Kidney Diseases / Q000151:congenital / Q000453:epidemiology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D019278:Matrix Metalloproteinase 3 / Q000235:genetics*; D020784:Matrix Metalloproteinase 8 / Q000235:genetics; D011110:Polymorphism, Genetic; D012306:Risk; D055771:Serbia / Q000453:epidemiology; D014517:Ureteral Obstruction / Q000453:epidemiology / Q000235:genetics; D014551:Urinary Tract / Q000002:abnormalities*; D014570:Urologic Diseases / Q000151:congenital / Q000453:epidemiology
chemical_list: D019278:Matrix Metalloproteinase 3; D020784:Matrix Metalloproteinase 8; D020781:Matrix Metalloproteinase 1