Posterior tibial tendinopathy associated with matrix metalloproteinase 13 promoter genotype and haplotype

• Published in: The journal of gene medicine Vol. 18; no. 11-12; pp. 325 - 330
• Main Authors: de Araujo Munhoz, Francielle Boçon, Baroneza, José Eduardo, Godoy-Santos, Alexandre, Fernandes, Túlio Diniz, Branco, Filipe Polese, Alle, Lupe Furtado, de Souza, Ricardo Lehtonen, dos Santos, Maria Cristina Leme Godoy
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.11.2016; Wiley Periodicals Inc
• Subjects: Case-Control Studies; Collagenase 3; Confidence intervals; Cross-Sectional Studies; Feet; Female; Gene Frequency; Gene polymorphism; Gene therapy; Genetic Association Studies; genetic polymorphism; Genetic Predisposition to Disease; Genotype & phenotype; haplotype; Haplotypes; Humans; Interstitial collagenase; Linkage Disequilibrium; Magnetic resonance imaging; Matrix metalloproteinase; Matrix Metalloproteinase 13 - genetics; Metalloproteinase; metalloproteinases; Middle Aged; Neutrophil collagenase; NMR; Nuclear magnetic resonance; Polymerase chain reaction; Polymorphism, Single Nucleotide; Posterior Tibial Tendon Dysfunction - genetics; Promoter Regions, Genetic; Restriction fragment length polymorphism; risk factor; Saliva; Sequence Analysis, DNA; Statistical analysis; tendinopathy; Tendinopathy - genetics; Tibia - pathology; metalloproteinases; haplotype; genetic polymorphism; risk factor; tendinopathy
• ISSN: 1099-498X; 1521-2254
• DOI: 10.1002/jgm.2934

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.