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研究生:吳欣哲
研究生(外文):Wu, Shin-Chie
論文名稱:台灣人群BMP-4, CXCL12及MCP-1基因多型性與牙周炎關係之探討
論文名稱(外文):BMP-4, CXCL12, and MCP-1 gene polymorphisms in Taiwanese Periodontitis Patients
指導教授:傅鍔傅鍔引用關係
指導教授(外文):Fu, Earl
口試委員:聶鑫楊安航傅鍔胡光宇江正陽
口試委員(外文):Nieh, ShinYang, An-HangFu, EarlHu, Kuang-YuChiang, Cheng-Yang
口試日期:2011-05-31
學位類別:碩士
校院名稱:國防醫學院
系所名稱:牙醫科學研究所
學門:醫藥衛生學門
學類:牙醫學類
論文種類:學術論文
論文出版年:2011
畢業學年度:99
語文別:中文
論文頁數:77
中文關鍵詞:牙周炎BMP-4趨化激素CXCL12MCP-1基因多型性
外文關鍵詞:periodontitisBMP-4chemokinesCXCL12MCP-1gene polymorphisms
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中文摘要
前言:牙周炎是一種慢性感染與發炎的疾病,是屬於一種多因子疾病,為人類最常罹患的疾病之一。包含微生物、環境、生活行為與系統性疾病等等因子會影響罹患中度到重度牙周炎。其特徵是有大量淋巴球細胞聚集在牙周病病灶區,造成許多不同種類的細胞激素釋放,疾病進展導致牙周囊袋產生以及牙周韌帶與齒槽骨等的牙周組織被破壞。近來研究顯示基因表現已被證實無論在慢性牙周炎或侵犯性牙周炎的罹病機制中扮演不可忽略的角色,尤以單一核苷酸多型性和疾病易感性的關係近年來一直受到高度重視。本次研究將針對BMP-4這個會影響骨骼及牙齒發育的基因以及兩種以證實在牙周疾病中會有表現的趨化激素CXCL12及MCP-1,檢驗其對牙周疾病易感性之關連性。另因BMP-4會影響牙齒發育,在下頷第一大臼齒常可發現具有遠心舌側牙根,故亦檢驗其基因多型性是否與牙根發育有明顯的關連性。其中在牙周炎與BMP-4及CXCL12基因多型性相關性的研究上尚未有文獻證實,另MCP-1基因多型性對台灣人群罹患牙周病的相關性亦未有研究指出。故本實驗將針對BMP-4 538 T/C、CXCL12 801 G/A及MCP-1 -2518 A/G這三個基因多型性的位置進行分析,以了解BMP-4、CXCL12及MCP-1之基因多型性與台灣人群罹患牙周病是否有相關性及BMP-4 538 T/C是否對下頷第一大臼齒遠心舌側牙根發育有關。
研究方法:實驗分為侵犯性牙周炎、慢性牙周炎及牙周健康三組。分別抽取個體周邊靜脈血,先將DNA分離出來後,以聚合酶鏈反應- 限制酵素片段長度多型性方法已得知BMP-4 538 T/C、CXCL12 801 G/A及MCP-1 -2518 A/G這三個基因多型性型態。另外也藉由問卷紀錄收案年齡、性別、抽菸、喝酒及嚼食檳榔等資料。下頷遠心舌側牙根的分析則以兩張不同角度的根尖片去做左右兩側的判讀。再以多變項對數迴歸分析比較各組間基因型與座基因的分布頻率。罹患牙周炎機會與基因型間的關係以危險比來表示。
結果:總共分析24位侵犯型牙周炎患者、137位慢性牙周炎患者及39位牙周健康的受試者。其中只有在年齡方面,明顯有侵犯性牙周炎患者及牙周健康組的年紀較慢性牙周炎患者來的輕(p<0.01)。在基因型頻率分布部分 BMP-4 538 T/C、CXCL12 801 G/A及MCP-1 -2518 A/G之間並無統計上差異。進一步針對侵犯性牙周炎、慢性牙周炎或是所有牙周炎(侵犯性加上慢性牙周炎)患者對於牙周健康者來比較,在BMP-4 538 T/C及MCP-1 -2518 A/G兩種基因型態皆無統計學上顯著差異。而在CXCL12 801 G/A部分,侵犯性牙周炎患者基因型態若為AA比起GG,其粗危險比只有0.304(p=0.038),再經過調整年齡、性別、抽菸等生活行為變項後,其危險比更只達0.186(p=0.013)。以AA+AG和GG來比較,再經過調整後危險比為0.227(p=0.021)。若以全部牙周炎的患者對健康族群患者來比較AA比起GG其調整後的危險比為0.368(p=0.033)。在對第一大臼齒遠心牙根發育型態與BMP-4 538 T/C基因型態的關連性方面,也無統計學上顯著差異。
結論:在CXCL12部分,801A 可能對於侵犯性牙周炎及整體性牙周疾病來說具有保護之作用,可能會減少疾病發生之機會。但在BMP-4 538 T/C及MCP-1 -2518 A/G兩種基因型態則對牙周炎疾病的易感性並無明顯關連性。BMP-4 538T/C亦跟下頷第一大臼齒遠心牙根發育無明顯關連性。

英文摘要(Abstract)
Introduction:Periodontitis is a chronic infection and inflammatory disease, which is a common disease. Periodontitis is a multifactorial disease, risks for moderate to severe periodontitis that have been identified include pecific pathogenic bacteria, environment, behavior and certain other systemic conditions. The great amount of lymphocytes which accumulated at site of periodontal lesion is characterized. The release of several cytokines results in the destruction of periodontium including periodontal pocket, periodontal ligment, and alveolar bone eventually. Many reviews have been published in recent years supporting the evidence that genes influence an individual’s predisposition for the initiation and progression of periodontal disease. A plethora of genetic factors, ranging from single gene defects to more subtle combinations of single nucleotide polymorphisms (SNPs), have been suggested as predisposing to aggressive periodontitis and chronic periodontitis. The present study was focus on BMP-4, which was important in bone and teeth formation, and the other two chemokines, CXCL12 and MCP-1 that changes level in periodontal disease. We could often find that mandibular first molar with distal lingual root. BMP-4 is one of genes that affect tooth development. We also investigated the association between BMP-4 gene polymorphism and root morphology.There was no study in relation between BMP-4, CXCL12 genotypes and periodontits. There was no MCP-1study in Taiwan reported such relationship between MCP-1 genotype and periodontitis either. Our aim was to evaluate whether the BMP-4 538 T/C, CXCL12 801 G/A and MCP-1 -2518 A/G gene polymorphisms were associated with periodontitis in a Taiwanese population.We also evaluated BMP-4 538T/C geneotype whether associated with mandibular first molar with distal lingual root.
Material and Methods:Subjects of our study were divide into three groups, namely aggressive periodontitis, chronic periodontitis, and healthy control according to clinical periodontal examination. The variants including gender, age, smoking status, alcoholic drinking and betel quid chewing were recorded.Genomic DNA was extracted from blood. Genotypes of BMP-4 538 T/C, CXCL12 801 G/A and MCP-1 -2518 A/G were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The mandibular first molars with distal lingual roots were determined by two periapical films which were in different angle. The data were analyzed by X2 test, one-way ANOVA amd multiple logistic regression analyses. The risk for periodontitis associated with genotypes was calculated as the odds ratio(OR).
Results:There are 24 people in aggressive periodontitis(AgP) group, 137 people in chronic periodontitis(CP) group, and 39 people in healthy control(H) group.In demographic data, only age in AP and H groups younger than CP groups(p<0.01). The association between BMP-4 538 T/C, CXCL12 801 G/A, MCP-1 -2518 A/G and AgP, CP, H groups were no significant difference. The further analysized AgP compared with H or CP compared H or all disease(AgP+CP) group compared with H.No matter any analysis, there were no significant difference between BMP-4 538 T/C, MCP-1 -2518 A/G and any other disease groups (p>0.05). In CXCL12 801 G/A, the prevalence of AA genotype compared with GG genotype was significantly lower in AgP. The crude OR and adjusted OR for AA versus GG in AgP group were 0.304 (p=0.038) and 0.186 (p=0.013) respectively. The adjusted OR for AA+AG versus GG in AgP group was 0.227(p=0.021). There was also significant difference that AA versus GG in all periodontal disease groups. The adjusted OR was 0.368(p=0.033). There was no difference between mandibular first molar with distal lingual root and BMP-4 genotype.
Conclusions:The results of this study suggested that CXCL12 801A seems to be associated with an decreased risk for aggressive periodontitis and all periodontal disease in a Taiwanese population. But there were no significant difference between BMP-4 538 T/C, MCP-1 -2518 A/G and susceptibility of periodontitis groups. There was no relation between BMP-4 538 T/C and mandibular first molar with distal lingual root either.

壹、 緒論 2
貳、 材料與方法 20
參、實驗結果 33
肆、討論 48
伍、結論 54
陸、參考文獻 67

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