title: Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children.
abstract: OBJECTIVE
  Matrix metalloproteinase-9 (MMP-9) is involved in the atherosclerotic process and functional polymorphisms in the MMP-9 gene affect MMP-9 expression/activity, and are associated with cardiovascular diseases. However, no study has tested the hypothesis that functional MMP-9 polymorphisms could affect MMP-9 levels in obese children. We investigated whether three MMP-9 gene polymorphisms (C-1562T (rs3918242), 90(CA)((14-24)) (rs2234681) and Q279R (rs17576)), or haplotypes, affect MMP-9 levels in obese children.
  
  
  METHODS
  We studied 175 healthy control children and 127 obese children. Plasma MMP-9, tissue inhibitor of MMPs (TIMP)-1 and adiponectin concentrations were measured using enzyme-linked immunosorbent assay.
  
  
  RESULTS
  We found similar MMP-9 genotypes, allelic and haplotypes distributions in the two study groups (P>0.05). However, we found lower plasma MMP-9 concentrations in obese subjects carrying the CC or the QQ genotypes for the C-1562T and the Q279R polymorphisms, respectively, in obese children compared with children with the other genotypes, or with non-obese children with the same genotypes (all P<0.05). Moreover, we found lower MMP-9 levels and lower MMP-9/TIMP-1 ratios (which reflect net MMP-9 activity) in obese children carrying the H2 haplotype (which combines the C, H and Q alleles for the three polymorphisms, respectively) when compared with obese children carrying the other haplotypes, or with non-obese children carrying the same haplotype (P<0.05).
  
  
  CONCLUSIONS
  Our findings show that MMP-9 genotypes and haplotypes affect MMP-9 levels in obese children and adolescents, and suggest that genetic factors may modify relevant pathogenetic mechanisms involved in the development of cardiovascular complications associated with obesity in childhood.
authors.affiliation: Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas, Campinas, Brazil.
authors.forename: V A
authors.initials: VA
authors.lastname: Belo
authors.forename: D C
authors.initials: DC
authors.lastname: Souza-Costa
authors.forename: M R
authors.initials: MR
authors.lastname: Luizon
authors.forename: C M M
authors.initials: CM
authors.lastname: Lanna
authors.forename: P C
authors.initials: PC
authors.lastname: Carneiro
authors.forename: T C
authors.initials: TC
authors.lastname: Izidoro-Toledo
authors.forename: K C
authors.initials: KC
authors.lastname: Ferraz
authors.forename: J E
authors.initials: JE
authors.lastname: Tanus-Santos
mesh_terms: D052242:Adiponectin / Q000097:blood; D002318:Cardiovascular Diseases / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood / Q000235:genetics*; D009765:Obesity / Q000097:blood / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood
chemical_list: D052242:Adiponectin; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9