title: Gene polymorphism -418 G/C of tissue inhibitor of metalloproteinases 2 is associated with abdominal aortic aneurysm.
abstract: OBJECTIVE
  The pathogenesis of abdominal aortic aneurysm (AAA) is connected with abnormal extracellular matrix remodeling, with the assistance of extracellular matrix metalloproteinases and tissue inhibitors of metalloproteinases (TIMPs). A decrease in tissue inhibitor of metalloproteinases 2 (TIMP2) gene expression was detected in AAA patients. Recently, a -418 G/C (rs8179090) polymorphism of the TIMP2 gene promoter, influencing the transcription rate of the gene, has been described. This study investigated whether the -418 G/C gene polymorphism is associated with AAA in the Polish population.
  
  
  METHODS
  The TIMP2 gene promoter polymorphism was evaluated by polymerase chain reaction, followed by restriction enzyme analysis and pyrosequencing in 128 patients affected by AAA and in 180 individuals included as references. The control group was directly matched to patients according to known risk factors for vascular diseases.
  
  
  RESULTS
  The frequency of the C allele was significantly higher in AAA patients than in the control group (odds ratio [OR], 2.516; P = .0005). The distribution of genotypes also differed significantly between the groups (CC + CG vs GG: OR, 2.906; P = .0037) or was close to being significantly different (CC vs GG + GC: OR, 2.144; P = .0501). A similar trend was observed in men but not in women. The multivariate logistic regression analysis indicated the TIMP2 gene promoter polymorphism is risk factor of AAA in the Polish population, with an adjusted OR of 4.99, when applied to a dominant inheritance model.
  
  
  CONCLUSIONS
  Our study supports the hypothesis that TIMP2 and the -418G/C polymorphism located in the promoter of the TIMP2 gene are important in AAA pathophysiology.
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland. Electronic address: joannastecyna@wp.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Mikołajczyk-Stecyna
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Korcz
authors.affiliation: Department of General and Vascular Surgery, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Gabriel
authors.affiliation: Department of Hypertension, Angiology and Internal Diseases, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pawlaczyk
authors.affiliation: Department of General and Vascular Surgery, Poznan University of Medical Sciences, Poznan, Poland.
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Oszkinis
authors.affiliation: Institute of Human Genetics, Polish Academy of Sciences, Poznan, Poland; Department of Biochemistry and Biotechnology, Poznan University of Life Sciences, Poznan, Poland.
authors.forename: Ryszard
authors.initials: R
authors.lastname: Słomski
mesh_terms: D000368:Aged; D000483:Alleles; D017544:Aortic Aneurysm, Abdominal / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011044:Poland; D011110:Polymorphism, Genetic / Q000235:genetics*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics*
chemical_list: D005819:Genetic Markers; C560823:TIMP2 protein, human; D019716:Tissue Inhibitor of Metalloproteinase-2