title: Analysis of MMP2 promoter polymorphisms in patients with pseudoxanthoma elasticum.
abstract: BACKGROUND
  Pseudoxanthoma elasticum (PXE) is a rare hereditary disorder predominantly affecting the skin, the eyes and the cardiovascular system. The disease is caused by mutations in the ABCC6 gene and characterized by ectopic calcification and extracellular matrix (ECM) alterations. Matrix metalloproteinases (MMPs) play a pivotal role in the process of ECM remodeling and are likely implied in PXE pathology. The aim of the present study was to investigate the association of single nucleotide polymorphisms (SNPs) in the promoter of the MMP2 gene, and PXE.
  
  
  METHODS
  We evaluated the allelic distribution of five SNPs in the MMP2 promoter in DNA samples from 168 German patients affected by PXE and in 168 healthy, age- and sex-matched control subjects using restriction fragment length polymorphism analysis.
  
  
  RESULTS
  The alleles c.-1575G, c.-1306C, and c.-790T were more abundant in the PXE patients' group. Furthermore, the haplotype GCTCG was significantly associated with PXE (OR 1.56, 95% CI 1.14-2.12, P(corrected)=0.026).
  
  
  CONCLUSIONS
  Our results may indicate an involvement of MMP2 in the pathology of PXE. The promoter polymorphisms associated with PXE may lead to increased MMP2 expression and thereby contribute to the elevated proteolytic activity observed in PXE in vitro and in vivo.
authors.affiliation: Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen, Universitätsklinik der Ruhr-Universität Bochum, Georgstrasse 11, 32545 Bad Oeynhausen, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Zarbock
authors.forename: Doris
authors.initials: D
authors.lastname: Hendig
authors.forename: Christiane
authors.initials: C
authors.lastname: Szliska
authors.forename: Knut
authors.initials: K
authors.lastname: Kleesiek
authors.forename: Christian
authors.initials: C
authors.lastname: Götting
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002114:Calcinosis; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins; D005260:Female; D005858:Germany; D006239:Haplotypes; D006801:Humans; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics*; D008875:Middle Aged; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011561:Pseudoxanthoma Elasticum / Q000235:genetics* / Q000473:pathology
chemical_list: D016326:Extracellular Matrix Proteins; D020778:Matrix Metalloproteinase 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C102029:ABCC6 protein, human; C522361:MMP2 protein, human