MMP-1, MMP-8, and MMP-13 Gene Polymorphisms and Haplotype Is a Risk Factor for Dupuytren Contracture: A Case-Control Study.

BACKGROUND: There is an increased tissue expression of matrix metalloproteinases (MMPs) on Dupuytren contracture (DC). Genetic polymorphisms (single nucleotide polymorphism [SNPs]) in genes of these enzymes may individually influence these transcriptions. Haplotype analysis, which is the observation of a group of alleles, could be more useful to identify the association between SNPs and DC. The purpose of this study was to evaluate the influence of MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs individually and in haplotype on DC. METHODS: A total of 60 patients with a clinical diagnosis of DC were evaluated and matched, according to age and gender, with the control group of 100 patients without this clinical diagnosis. Genomic DNA was extracted from saliva samples, and genotypes were obtained by polymerase chain reaction-restriction fragment length polymorphism. Statistical analysis of the results included Mann-Whitney U test, Chi-squared test, and PHASE and R software, with a significance level of 5%. RESULTS: The 3 SNPs studied showed significant differences in allele and genotype frequencies between the groups: 2G in MMP-1 (P = .018; odds ratio [OR] 1.80 (95% confidence interval [CI], 1.13-2.88)), T in MMP-8 (P = .015; OR 0.53 (95% CI, 0.33-0.88)), and A in MMP-13 (rs2252070) SNPs (P = .040, OR 0.54 (95% CI, 0.33-0.90)) are risk alleles. The global haplotype analysis indicated a significant difference between both groups. CONCLUSIONS: In conclusion, MMP-1 g.-1607 G>GG (rs1799750), MMP-8 g.-799 C>T (rs11225395), and MMP-13 g.-77 A>G (rs2252070) SNPs, individually and in haplotype, are a risk factor for DC, indicating that these SNPs may be a potential diagnostic and prognostic factor for DC.

Matrix Metalloproteases 1 and 3 Promoter Gene Polymorphism Is Associated With Rotator Cuff Tear.

BACKGROUND: Studies suggest that the collagen degeneration and disordered arrangement of collagen fibers in rotator cuff tears are associated with an increase in activity of matrix metalloproteases 1 and 3 (MMP-1 and MMP-3), and that MMP activity may be in part genetically mediated. The degree to which this might be clinically relevant in patients with rotator cuff tears has not been well characterized. QUESTIONS/PURPOSES: (1) Is genetic polymorphism of MMP-1 and MMP-3 associated with rotator cuff tears? (2) Are there haplotypes of MMP-1 and MMP-3 correlated with rotator cuff tears? (3) Compared with control subjects, do patients with rotator cuff tears have a higher proportion of relatives with the same disease? METHODS: We evaluated 64 patients with full-thickness rotator cuff tears and 64 asymptomatic control subjects. Patients younger 65 years, with nontraumatic tears, were included. The tear or integrity of the rotator cuff tear was evaluated by MRI or ultrasonography in all individuals. The patients and control subjects were paired by age. MMP-1 and MMP-3 genotypes were determined using the PCR-restriction fragment length polymorphism assays. RESULTS: Genetic polymorphisms in MMP-1 and MMP-3 are associated with rotator cuff tear, in which individuals with rotator cuff tears have associated genotypes 1G/2G (patients, 32 of 64 [50%], control subjects, 16 of 64 [25%]; odds ratio [OR], 4.8; 95% CI, 2.1-11.0; p < 0.001) and 2G/2G were at great risk (patients, 15 of 64 [23%], control subjects, seven of 64 [11%]; OR, 5.2; 95% CI,1.8-14.9; p < 0.001), and patients with rotator cuff tears were associated with a higher proportion of 2G allele distribution (62 of 128 [48%] versus 30 of 128 [23%]; p < 0.001). Patients with the 5A/5A genotype are at greater risk of rotator cuff tear (patients, 15 of 64 [23%]; control subjects, four of 64 [6%]; OR, 5.5; 95% CI, 1.4-20.9; p = 0.021), and there was higher 5A allele distribution in patients with rotator cuff tears (patients, 68 of 128 [53%]; control subjects, 52 of 128 [41%]; p = 0.045). Individuals with the haplotype 2G/5A were more likely to have rotator cuff tears develop (patients, 42 of 64 [66%]; control subjects, 17 of 64 [27%]; OR, 5.3; 95% CI, 2.5-11.3; p < 0.001). Patients with rotator cuff tears reported, in higher number, the existence of relatives who previously had treatment for rotator cuff tears (19 of 64 [30%] versus four of 64 [6%]; OR, 6.3; 95% CI, 2.0-19.9; p = 0.001). CONCLUSIONS: The genetic polymorphism of MMP-1 and MMP-3 is associated with rotator cuff tear. Individuals with haplotype 2G/5A were more susceptible to rotator cuff tears in the population studied. CLINICAL RELEVANCE: Knowledge of the genetic markers related to rotator cuff tears can enable identification of susceptible individuals and increase understanding of the pathogenesis of tendon degeneration.

MMP-1 promoter polymorphism is associated with primary tendinopathy of the posterior tibial tendon.

Posterior tibial tendon (PTT) dysfunction is recognized as an etiology leading to acquired flatfoot in adults, causing significant functional loss. Many risk factors and systemic conditions have been proposed in literature. However, many patients present PTT dysfunction without any of these characteristics. This suggests that there could be a genetic influence associated with posterior tibial tendinopathy. The purpose of the present study is to investigate the association of the -1607 polymorphism in the promoter gene of MMP-1 and posterior tibial tendinopathy. The test group included 50 women, who presented PTT dysfunction grade 2 or 3, and who were submitted to surgical treatment, with histopathological examination of the tendon and magnetic resonance image (MRI) confirming tendinopathy, while the control group was 100 asymptomatic women who presented intact PTT at MRI. The results were analyzed using the chi-square test. The data showed a 75% incidence of the allele 1G and 62% of the genotype 1G/1G at the control group while, at the test group, they showed a 78% incidence of the allele 2G and 72% of the genotype 2G/2G (p < 0.001). The -1607 polymorphism of promoter gene of MMP-1 is associated with the posterior tibial tendinopathy in the studied population.

Influence of MMP-8 promoter polymorphism in early osseointegrated implant failure.

OBJECTIVE: Dental implants consist in the treatment of choice to replace tooth loss. The knowledge that implant loss tends to cluster in subsets of individuals may indicate that host immuneinflammatory response is influenced by genetic factors. In fact, genetic polymorphisms influence the osseointegration process. The objective of this study was investigate the possible relationship between C-799T polymorphism in matrix metalloproteinase 8 (MMP-8) gene and early implant failure in nonsmoker patients. METHODS AND MATERIALS: Subjects were divided into two groups: control group (100 patients with one or more healthy implants) and test group (80 patients that had suffered one or more early implant failures). Genomic DNA from oral mucosa was amplified by PCR and analyzed by restriction endonucleases. The significance of the differences in observed frequencies of polymorphisms was assessed by Chi-square. RESULTS: Statistical analysis shows that in the MMP-8 gene, the T allele in 76.25% in the test group and the T/T genotype, 63.75% in the same group, may predispose to early loss of implants osseointegrated. CONCLUSION: These results suggest that polymorphism in the promoter region of MMP-8 gene is associated with early implant failure. This polymorphism can be a genetic marker to risk of implant loss. CLINICAL RELEVANCE: The determination of this genetic pattern in osseointegration would enable the identification of individuals at higher risk to loss implant. Thus, genetic markers will be identified, contributing to an appropriate preoperative selection and preparation of strategies for prevention and therapy individualized to modulate the genetic markers and increase the success rate of treatments.

Perda de implante osseointegrado: fatores ligados ao hospedeiro / Loss of osteointegrated implant: host related factors

Nos últimos anos, o sucesso da osseointegração tornou a instalação de implantes osseointegrados uma opção viável para o tratamento de diversas situações de edentulismo, uma vez que confere um bom resultado estético e funcional. Apesar do alto índice de sucesso desses implantes, falhas ainda ocorrem. A perda do implante osseointegrado pode ser caracterizado como precoce, quando ocorre durante o período de osseointegração, ou tardia, que acontece após o implante ser submetido a cargas oclusais. Ainda não são claros as causas e os mecanismos dos diferentes fatores associados à perda dos implantes. O fenômeno em cacho, no qual alguns pacientes sofrem múltiplas perdas, suporta a evidência que a característica individual tem um papel importante na osseointegração. Entretanto pouco se sabe sobre a influência genética na susceptibilidade a perda precoce de implantes osseointegrados. Polimorfismos são variações genéticas encontradas na população, consideradas dentro da normalidade, que tornam um indivíduo mais ou menos suscetível a uma determinada patalogia. Desde que polimorfismos genéticos podem alterar a transcrição de mediadores inflamatórios sua análise pode promover um efeito monitoramento da osseointegração.