title: Posterior tibial tendinopathy associated with matrix metalloproteinase 13 promoter genotype and haplotype.
abstract: BACKGROUND
  Posterior tibial tendon (PTT) is particularly vulnerable and its insufficiency is recognized as the main cause of adult acquired flat foot. Some patients have a predisposition without a clinically recognized cause, suggesting that individual characteristics play an important role in tendinopathy. The present study investigated whether genetic variants in matrix metalloproteinases (MMPs) are associated with PTT dysfunction.
  
  
  METHODS
  One hundred women who presented PTT dysfunction, with histopathological examination of the tendon and magnetic resonance imaging (MRI) confirming tendinopathy, as well as 100 asymptomatic women who presented intact PPT as assessed by MRI and constituting the control group, were evaluated for MMP-13 g.-77 A > G (rs2252070) polymorphism, individually and in haplotypes, as well as in combination with MMP-1 g.-519 A > G (rs1144393), MMP-1 g.-1607 G > GG (rs1799750) and MMP-8 g.-799 C > T (rs11225395) polymorphisms with PTT dysfunction. Genomic DNA was extracted from the saliva and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included a Mann-Whitney U-test, Fisher's exact test, multiple logistic regression, chi-squared and SNPstats software (http://bioinfo. iconcologia.net/snpstats/start.htm). p < 0.05 was considered statistically significant.
  
  
  RESULTS
  The A allele frequency (MMP-13 g.-77 A > G (rs2252070) polymorphism) was significantly higher in the case group (76% and 61%, respectively; p = 0.010, odds ratio = 2.02; 95% confidence interval = 1.32-3.12). The genotype distribution was also significantly different between groups (p = 0.001, odds ratio = 2.82; 95% confidence interval = 1.58-5.02). Global haplotype analysis indicated a significant difference between both groups.
  
  
  CONCLUSIONS
  In conclusion, these findings indicate that MMP-13 g.-77 A > G (rs2252070) polymorphism individually, as well as its haplotypes MMP-1 g.-519 A > G (rs1144393), MMP-1 g.-1607 G > GG (rs1799750) and MMP-8 g.-799 C > T (rs11225395), may contribute to PTT dysfunction.
authors.affiliation: Department of Cell Biology, University Federal of Paraná, Curitiba, Puerto Rico, Brazil.
authors.forename: Francielle Boçon
authors.initials: FB
authors.lastname: de Araujo Munhoz
authors.affiliation: Department of Cell Biology, University Federal of Paraná, Curitiba, Puerto Rico, Brazil.
authors.forename: José Eduardo
authors.initials: JE
authors.lastname: Baroneza
authors.affiliation: Department of Orthopedics and Traumatology, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Godoy-Santos
authors.affiliation: Department of Orthopedics and Traumatology, University of São Paulo, São Paulo, SP, Brazil.
authors.forename: Túlio Diniz
authors.initials: TD
authors.lastname: Fernandes
authors.affiliation: Avantis Faculty of Balneário Camboriú, Balneário Camboriú, South Carolina, Brazil.
authors.forename: Filipe Polese
authors.initials: FP
authors.lastname: Branco
authors.affiliation: Department of Genetic, University Federal of Paraná, Curitiba, Puerto Rico, Brazil.
authors.forename: Lupe Furtado
authors.initials: LF
authors.lastname: Alle
authors.affiliation: Department of Genetic, University Federal of Paraná, Curitiba, Puerto Rico, Brazil.
authors.forename: Ricardo Lehtonen
authors.initials: RL
authors.lastname: de Souza
authors.affiliation: Department of Cell Biology, University Federal of Paraná, Curitiba, Puerto Rico, Brazil.
authors.forename: Maria Cristina Leme Godoy
authors.initials: MC
authors.lastname: Dos Santos
mesh_terms: D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D005260:Female; D005787:Gene Frequency; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D053509:Matrix Metalloproteinase 13 / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D037081:Posterior Tibial Tendon Dysfunction / Q000235:genetics*; D011401:Promoter Regions, Genetic; D017422:Sequence Analysis, DNA; D052256:Tendinopathy / Q000235:genetics*; D013977:Tibia / Q000473:pathology
chemical_list: C507079:MMP13 protein, human; D053509:Matrix Metalloproteinase 13
keywords: genetic polymorphism; haplotype; metalloproteinases; risk factor; tendinopathy