MMPs與牙周組織的破壞有強?的相關性，因為MMPs是牙周組織的破壞時，膠原蛋白纖維破壞的重要介質。許多有關MMPs及TIMPs的基因多型性的研究探討它們與牙周炎的感受性及/或嚴重性。有些過去的研究探討牙周炎的感受性與多種 interleukins 基因多型性的關係。牙周細胞積極?與innate immune response 以對抗牙菌斑細菌，牙周細胞會表現各種的Toll-like receptors(TLRs)。TLRs的訊息傳遞結果使innate immune response 釋出anti-bacterial peptide及募集neutrophils的IL-8 ，因此TLRs的表現可謂是對細菌的侵犯時，激發炎性反應的工具，顯示TLRs在牙周炎扮演某一角色。 TLRs的基因多型性與牙周炎的感受性在一些族群亦有被探討。基因在宿主的免疫反應上具有一定的角色，但結果在族群間顯示有極大的差?。本計畫將對感受性基因，包括MMP-1、-2、-3、-8、-9及-12，TIMP-1、-2，IL-2、-4、-8、-17，CD14、TLR-2、TLR-4以polymerase chain-restriction fragment length polymorphism analysis?探討。同時探討基因的nucleotide transition對宿主細胞激素(炎性介質)的表現(protein or mRNA)的影響。在過去的基因研究也有注意到對免疫調整(immune regulation )或新陳代謝(metabolism)有關的細胞激素(介質)與牙周炎感受性的角色，但與功能上的表現(functional implication)的關係的研究報告則尚缺乏。本計畫也要在基因多型性與牙周炎的關係間提供功能上的證據(functional evidence) ，這可藉由分析牙周炎患者全血細胞培養液的細胞激素(介質)濃?偵測得知，?用ELISA偵測protein expression, RT-PCR偵測mRNA expression。
MMPs have strong correlation to periodontal diseases, since MMPs are the major players in collagen breakdown during periodontal tissue destruction. Some studies in the past years had indicated the association between selected candidate gene polymorphisms and the susceptibility to periodontitis. The TLR signaling results in innate immune responses involving the release of antibacterial peptides and neutrophil recruiting chemokine (IL-8). TLR signaling serves to limit pathogenic infections and to prevent commensal organisms from breaching the epithelial barrier. In the epithelium and connective tissue via TLR signaling, the stimulated cells could produce an array of cytokines, chemokines, and other mediators that promote inflammation and immune cell infiltration. Additional cytokines produced by infiltrated memory T cells would amplify the inflammatory reaction, leading to destruction of connective tissue and bone. Investigation into TLR SNPs in periodontitis individuals should provide some insight into the role of the immune system in maintaining periodontal health and combating periodontal disease. During the past few years, several genes have been individually sequenced for association with periodontitis. Different studies have been conducted in varied populations and ethnicities. Frequencies of the genetic marker of interest may show large heterogenecity between races Variation in genotype frequencies across diverse population may affect the number of individuals at increased risk for a disease, and population substructure imbalances may create serious differences in genotype frequencies of the compared groups in gene-disease association studies Susceptible genes polymorphisms including MMPs(MMP-1、-2、-3、-8、-9 and -12)，TIMPs (TIMP-1、-2)、interleukin(IL-2、-4、-8、-17)、antigen-recognition-related receptors(CD14、TLR-2、TLR-4) shall be analyzed by polymerase chain-restriction fragment length polymorphism analysis. We shall also investigate whether the nucleotide transition will affect the protein and mRNA expressions of the cytokines/mediators which shall be analyzed with ELISA in the samples of the supernatants and RT-PCR of the cell lysates of whole-blood cell cultures respectively. Our data shall provide functional evidence in the association between selected gene plomoyphisms and the susceptibility to periodontitis.
