title: Evaluation of genetic variation and association in the matrix metalloproteinase 9 (MMP9) gene in ESRD patients.
abstract: BACKGROUND
  Matrix metalloproteinases are Zn2+- and Ca2+-dependent endopeptidases secreted by many cells. Expression of the matrix metalloproteinase 9 (MMP9) gene is increased in a variety of renal diseases. Several genetic studies have associated MMP9 with end-stage renal disease (ESRD).
  
  
  METHODS
  In this study, 2.2 kb of the promoter region and all 13 exons (3.3 kb) of MMP9 genomic DNA were scanned for polymorphisms. Genetic associations between MMP9 polymorphisms and renal disease were evaluated.
  
  
  RESULTS
  Eleven single-nucleotide polymorphisms (SNPs; 4 promoter, 6 coding region, and 1 3' untranslated region [UTR]) were identified in Caucasians and 19 SNPs (11 promoter, 8 coding region, 1 3' UTR) were identified in African Americans. A previously identified highly polymorphic (CA)n repeat in the promoter region of MMP9 also was evaluated. We found 15 alleles in Caucasians and 14 alleles in African Americans. Allele frequencies, genotypes, and 3-marker haplotypes were compared between patient and control populations. Differences were not observed using single-locus analyses. Two haplotypes that included the (CA)n repeat allele in African-American patients with type 2 diabetic nephropathy (T2DM/ESRD) showed borderline significant differences. Dichotomizing the (CA)n repeat distribution showed that shorter alleles in Caucasian cases were associated with ESRD using an additive disease-predisposing model (P = 0.05). Analysis of the (CA)n repeat in expanded sets of subjects showed strong evidence for an association of shorter alleles with ESRD in Caucasians (P = 0.00012) and suggested a similar trend in African Americans with T2DM/ESRD (P = 0.086) and subjects without T2DM/ESRD (P = 0.047).
  
  
  CONCLUSIONS
  This comprehensive analysis of MMP9 and renal disease suggests a possible role for the (CA)n repeat in renal disease, consistent with previous reports.
authors.affiliation: Department of Biochemistry, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
authors.forename: Shohei
authors.initials: S
authors.lastname: Hirakawa
authors.forename: Ethan M
authors.initials: EM
authors.lastname: Lange
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Colicigno
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Stephen S
authors.initials: SS
authors.lastname: Rich
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000483:Alleles; D019943:Amino Acid Substitution; D044383:Black People / Q000235:genetics; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000201:enzymology / Q000235:genetics*; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000235:genetics*; D005091:Exons / Q000235:genetics; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000201:enzymology / Q000235:genetics* / Q000628:therapy; D015810:Linkage Disequilibrium; D020780:Matrix Metalloproteinase 9 / Q000235:genetics* / Q000502:physiology; D018598:Minisatellite Repeats; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D006435:Renal Dialysis; D044465:White People / Q000235:genetics; D001741:Black or African American
chemical_list: D020413:3' Untranslated Regions; D020780:Matrix Metalloproteinase 9