Matrix metalloproteinases gene polymorphism haplotype is a risk factor to implant loss: A case-control study.

BACKGROUND: 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 response is influenced by genetic factors. Matrix metalloproteinases (MMPs) are enzymes that contribute to degradation and removal of collagen from extracellular matrix. PURPOSE: This case-control study aimed to investigate the haplotypic combination of MMP polymorphism (rs1144393, rs1799750, rs3025058, and rs11225395) and implant loss. MATERIALS AND METHODS: Two hundred nonsmokers subjects were matched by gender, age, implant number and position and divided in control group, 100 patients with one or more healthy implants, and test group, and 100 patients with one or more implant failures. Genomic DNA was extracted from saliva and genotypes were obtained by PCR-RFLP. RESULTS: A significant association of rs1799750 (MMP-1) and rs11225395 (MMP-8) polymorphism on early implant loss was demonstrated (P ≤ 0.001). Global haplotype analysis indicated a significant difference between both groups (P < 0.0001). Haplotype T-A-GG-5A-C had a statistically significant risk effect, while haplotype C-A-G-6A-C andT-G-2G-5A-C had a protective effect in implant loss. CONCLUSIONS: The results of this study showed that MMPs haplotype are a risk factor to early implant loss.

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

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.

Analysis of the transforming growth factor-beta 1 gene promoter polymorphisms in early osseointegrated implant failure.

Transforming growth factor-beta 1 is a multifunctional cytokine involved in extracellular matrix deposition, reduction of inflammation, and promotion of wound healing. Single nucleotide polymorphisms in the promoter region of human transforming growth factor-beta 1 gene, C-509T and G-800A, have been shown to increase the transcriptional activity of this cytokine and have been associated with a variety of diseases. The objective of this study was to investigate the possible association between these single nucleotide polymorphisms and the early implant failure. A sample of 68 nonsmoking patients was divided into two groups: a test group comprising 28 patients with one or more early failed implants and a control group consisting of 40 individuals with one or more healthy implants. Genomic DNA from oral mucosa was amplified by polymerase chain reaction and analyzed by restriction fragment length polymorphism. The significance of the differences in observed frequencies of single nucleotide polymorphisms was assessed using the chi square test and Fisher's exact test. The cited single nucleotide polymorphisms in transforming growth factor-beta 1 were analyzed in combination as haplotype using the computer program ARLEQUIN. The authors did not observe significant differences in the allele and genotypes to both single nucleotide polymorphisms of transforming growth factor-beta 1 gene (C-509T and G-800A) between control and early implant failure groups. The distribution of the haplotypes arranged as allele and genotypes were similar between control and test groups. These results indicate that C-509T and G-800A polymorphisms in the transforming growth factor-beta 1 gene are not associated separately or in haplotype combinations with early implant failure, suggesting that the presence of those single nucleotide polymorphisms alone do not constitute a genetic risk factor for early implant failure in the Brazilian population.

Early failure of dental implants and TNF-alpha (G-308A) gene polymorphism.

Tumor necrosis factor-alpha (TNF-alpha) is a potent inflammatory mediator with bone resorption activity. Polymorphisms in the promoter region of the human TNF-alpha gene have been shown to affect the levels of this cytokine and have been associated with a variety of diseases. The aim of this study was to investigate the possible relationship between early implant failure and a single nucleotide polymorphism (SNP) in the -308 promoter region of the TNF-alpha gene. A sample of 66 nonsmokers was divided into 2 groups: a test group comprising 28 patients (mean age, 52.7 years) with one or more early failed implants and a control group consisting of 38 individuals (mean age, 43.2 years) with one or more healthy implants. Genomic DNA from buccal mucosa was amplified by the polymerase chain reaction (PCR), analyzed by restriction fragment length polymorphism (RFLP), and submitted to polyacrylamide gel electrophoresis to distinguish allele G and allele A of the TNF-alpha (-308) gene polymorphism. Differences in the allele and genotype frequencies between control and test groups were assessed by chi-squared test (P <0.05). No significant difference was observed in the allele (P = 0.4635) and genotype (P = 0.4445) distribution of the polymorphism when control and failure groups were compared. The results indicate that the TNF-alpha (G-308A) gene polymorphism is not associated with early implant failure, suggesting that its presence alone does not constitute a genetic risk factor for implant loss in the Brazilian population.