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Title: Posterior tibial tendinopathy associated with matrix metalloproteinase 13 promoter genotype and haplotype.
Author: de Araujo Munhoz FB, Baroneza JE, Godoy-Santos A, Fernandes TD, Branco FP, Alle LF, de Souza RL, Dos Santos MC.
Journal: J Gene Med; 2016 Nov; 18(11-12):325-330. PubMed ID: 27886420.
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.

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