Resumen de Quantitative Analysis of Interdental Gingiva in Patients With Chronic Periodontitis and Transforming Growth Factor-ß1 29C/T Gene Polymorphisms
Background: The association of transforming growth factor (TGF)-ß1 29C/T gene polymorphisms with level of tissue breakdown and periodontal disease progression is not clear. In this study, quantitative parameters of interdental papilla are investigated in patients with chronic periodontitis (CP) and TGF-ß1 29C/T gene polymorphisms.
Methods: Sixty gingiva samples were included. After determination of TGF-ß1 29C/T gene polymorphisms using tetra-primer amplification refractory mutation system/polymerase chain reaction (T-ARMS-PCR), 15 gingival tissue samples from patients with CP in each genotype (TT, TC, and CC) were considered as case groups. Fifteen control samples were also collected from healthy individuals. After tissue processing, interdental gingiva tissues were exhaustively sectioned into 4-µm-thick sections. Ten to 13 sections were sampled by systematic uniform random sampling and stained with Masson trichrome, and the volume density (Vv) of the gingival components was estimated using Cavalieri estimation.
Results: Statistically significant differences were found in Vv of epithelium, connective tissue, collagenous and non-collagenous matrix, and blood vessels between control and CP groups (P <0.0001). There was a corresponding decrease in the collagenous matrix Vv in patients with the TT genotype compared with those with CT and CC genotypes. Collagenous matrix and blood vessel Vv values were statistically correlated with the number of T alleles (r = -0.74, r2 = 54.8%, P = 0.0001 and r = 0.84, r2 = 70.6%, P = 0.0001, respectively).
Conclusion: This study shows that there is a strong association between TGF-ß1 29C/T gene polymorphisms and quantitative parameters of interdental papilla in patients with CP.
Chronic periodontitis (CP) is a common complex infectious disease that leads to the breakdown of the periodontal tissues and tooth loss.1 It is histologically characterized by the degradation of extracellular matrix components associated with an infiltration of several inflammatory cell populations into the gingival epithelium and connective tissue.2,3 The pathogenesis of periodontitis depends on the interactions between host and microorganism and may be complicated by genetic and environmental risk factors.4 With continued chronic inflammation, numerous autocrine and paracrine loops of cytokines act on the cells within the lesion. These cells are subject to many extracellular stimuli, whereas only a handful of inducible transcription factors appear to play crucial roles in the regulation of inflammatory genes.5 Cytokine networks play an important role in the initiation and progression of periodontal disease. Proinflammatory cytokines play crucial roles in microbe-induced destructive inflammation.6 During the progression of periodontal inflammation, periodontal ligament and gingival fibroblasts secrete high levels of cytokines and chemokines. Transforming growth factor (TGF)-ß1 is a highly conserved and ubiquitously expressed cytokine, and most cells express members of the TGF-ß1 receptor family. TGF is credited for promoting wound fibroblasts to differentiate at sites of inflammation and repair.7 On the other hand, studies linking apoptotic cell recognition and clearance report an induction of TGF-ß1 secretion, resulting in accelerated resolution of inflammation.8,9 TGF-ß1 controls the initiation and resolution of inflammatory responses through the regulation of chemotaxis, activation, and survival of cells involved in this process.10 In the periodontium, TGF-ß1 suppresses proteolytic activity by downregulating the transcriptional activity of matrix metalloproteinases (MMPs) and activates the expression of tissue inhibitors of MMPs (TIMPs).11,12 TGF-ß1 can stimulate the synthesis of connective tissue matrix components by fibroblasts and osteoblasts.13,14 This results in the formation of extracellular matrix and induces fibrosis. On the other hand, TGF-ß1 was shown to induce chemotaxis for neutrophils, monocytes, mast cells, and lymphocytes. It may also increase the release of leukocyte cytokines, which could contribute to the breakdown of periodontal tissue, especially in early phases of the inflammatory response.15 Evidence shows that the concentration of active TGF-ß1 may be predominantly under genetic control but its mechanism is poorly understood.15,16 Studies have reported that some cytokines are encoded by polymorphic genes, showing genotypes associated with inflammatory diseases that may confer susceptibility to periodontal disease.17,18 These molecules contribute to the breakdown of type I collagen and also promote bone resorption by stimulating proliferation, differentiation, and activation of osteoclasts.15,19,20 A polymorphism that has been described in the TGF-ß1 gene (TGFB1) is 29 C/T (Pro10Leu). It has been demonstrated that TT homozygous genotypes are high TGF-ß1 producers.21 A previous study by the present authors showed that CT and TT genotypes of TGFB1 (29 C/T) increase the risk of CP in comparison with the CC genotype, and the T allele increased the risk of CP in comparison with the C allele.22 More studies are required to verify the association of TGF-ß1 polymorphisms with level of tissue breakdown and periodontal disease progression. To date, there are no data concerning the quantitative parameters of gingival tissues of individuals with TGFB1 polymorphisms. In the present study, quantitative parameters of interdental gingiva in patients with CP with TGF-ß1 29C/T gene polymorphisms are investigated.
