title: Matrix metalloproteinase-9 gene polymorphisms and chronic kidney disease.
abstract: BACKGROUND
  The aim of this study was to explore the associations between the prevalence of chronic kidney disease (CKD) and polymorphisms in the genes encoding matrix metalloproteinases (MMPs) and tissue inhibitor of matrix metalloproteinases (TIMPs). MMPs degrade extracellular matrix proteins in the glomerulus, and play important roles in kidney disease progression.
  
  
  METHODS
  DNA samples from 3,309 subjects aged 35-69 years were genotyped for 10 potentially functional polymorphisms in MMP and TIMP genes. The prevalence of CKD (estimated glomerular filtration rate <60 ml/min/1.73 m(2)) was compared among the genotypes.
  
  
  RESULTS
  The prevalence of CKD decreased significantly with the number of minor alleles in MMP9 C-1562T (odds ratios (ORs) 0.77 for CT and 0.65 for TT compared with CC; p for trend = 0.023) and MMP9 R668Q (ORs, 0.79 for RQ and 0.64 for QQ compared with RR; p for trend = 0.024). The haplotype MMP9 -1562T/279R/668Q showed a reduced risk for CKD compared with the most common -1562C/279R/668R (OR 0.77, p = 0.008), and the genotype combination -1562TT/ 279RR/668QQ showed a halved risk for CKD compared with major allele homozygous -1562CC/279RR/668RR (OR 0.53, p = 0.091).
  
  
  CONCLUSIONS
  The potentially functional polymorphisms of MMP9 were associated with the prevalence of CKD in a large Japanese population. These genotypes have been reported to increase MMP9 expression, supporting the hypothesis that MMP-9 has a protective role in the progression of kidney diseases.
authors.affiliation: Department of Preventive Medicine, Nagoya University Graduate School of Medicine, Japan. rieokada@med.nagoya-u.ac.jp
authors.forename: Rieko
authors.initials: R
authors.lastname: Okada
authors.forename: Sayo
authors.initials: S
authors.lastname: Kawai
authors.forename: Mariko
authors.initials: M
authors.lastname: Naito
authors.forename: Asahi
authors.initials: A
authors.lastname: Hishida
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Hamajima
authors.forename: Koichi
authors.initials: K
authors.lastname: Shinchi
authors.forename: Tanvir
authors.initials: T
authors.lastname: Chowdhury Turin
authors.forename: Sadao
authors.initials: S
authors.lastname: Suzuki
authors.forename: Eva Mariane
authors.initials: EM
authors.lastname: Mantjoro
authors.forename: Kengo
authors.initials: K
authors.lastname: Toyomura
authors.forename: Kokichi
authors.initials: K
authors.lastname: Arisawa
authors.forename: Nagato
authors.initials: N
authors.lastname: Kuriyama
authors.forename: Satoyo
authors.initials: S
authors.lastname: Hosono
authors.forename: Haruo
authors.initials: H
authors.lastname: Mikami
authors.forename: Michiaki
authors.initials: M
authors.lastname: Kubo
authors.forename: Hideo
authors.initials: H
authors.lastname: Tanaka
authors.forename: Kenji
authors.initials: K
authors.lastname: Wakai
mesh_terms: D000328:Adult; D000368:Aged; D003430:Cross-Sectional Studies; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000235:genetics*; D008875:Middle Aged; D011110:Polymorphism, Genetic; D015995:Prevalence; D051436:Renal Insufficiency, Chronic / Q000453:epidemiology* / Q000235:genetics*; D019714:Tissue Inhibitor of Metalloproteinases / Q000235:genetics*
chemical_list: D019714:Tissue Inhibitor of Metalloproteinases; D020780:Matrix Metalloproteinase 9