台灣漢族華人牙周炎和 CD14-159基因多型性相關性

The Association of CD14 -159 Gene Polymorphism and Periodontal Disease in a Taiwan Han Population

陳建輔(Chien-Fu Chen)

指導教授 ： 何坤炎

高雄醫學大學/口腔醫學院/牙醫學研究所/碩士(2012年)

https://doi.org/10.6832/KMU.2012.00060

摘要

研究目的
牙周病是由細菌引起的發炎疾病，其中格蘭氏陰性菌細胞壁上lipopolysaccharide (LPS)的釋放所誘發的免疫反應扮演重要的角色，而CD14分子是LPS的一種受器，參與活化細菌入侵產生innate immune response。過去的研究指出牙周炎的感受性與免疫反應相關基因的基因多型性(genetic polymorphisms)有關，目前CD14基因多型性對台灣地區漢族人牙周炎的易感受性仍然不清楚。
實驗材料與方法
總共有270位受試者，慢性牙周炎(CP)(N=122)、侵犯型牙周炎(AgP)(N=84)病人及無家族相關性的健康對照組(HC)(N=64)為收案對象，所有個案均為台灣漢族且至少具有18顆自然牙。牙周疾病的診斷依據為西元1999年世界牙周病研討會及美國牙周病醫學會所頒佈的條件。個案靜脈周邊血樣本供萃取genomic DNA所需，以Real-time Taqman Probe PCR方法進行CD14 -159C>T(rs2569190)基因多型性檢測。受試者在收案前須先取得受試者同意書，再進行健康問卷調查收集受試者的家族病史、臨床醫療紀錄，以及抽菸、喝酒、嚼食檳榔等習慣和抽血。研究利用卡方檢定(χ2 test)檢定樣本基因分布與不同疾病診斷有無差異，並利用多變項邏輯式複迴歸分析（Multiple Logistic Regression）分析影響有無罹患牙周炎與CD14基因多型性的相關性。
結果
初步結果發現CD14(rs2569190)基因型CC出現頻率較低，因此統計處理將CC基因型與CT基因型合併討論。CD14基因型在慢性牙周炎和牙周健康組兩者間統計學上未達顯著差異；在侵犯性牙周炎及牙周健康組間亦未達顯著統計學上差異。若單純以樣本中未吸菸者進行統計分析，CD14基因型在慢性牙周炎和牙周健康組這兩者間統計學上達顯著的差異(p=0.0466)，其中基因型CT+CC的受試者較基因型TT的受試者易出現慢性牙周炎的機率，為0.41倍。同樣以未吸菸者之樣本進行CD14基因型在侵犯性牙周炎與健康組別之統計學討論，則未達統計學上顯著差異。
結論
本研究結果顯示CD14 -159基因多型性可能與國人未吸菸者罹患慢性牙周炎之易感性有關。帶有 T allele 基因型的患者罹患慢性牙周炎之危險性增加。但基因型差異在罹病機率角色上會被抽菸行為所覆蓋。

關鍵字

CD14 ； 基因多型性 ； 慢性牙周炎 ； 侵犯性牙周炎

並列摘要

Objectives : Studies have shown that genetic factors can account for a large part of the variation seen in periodontal disease expression in humans. CD14, a glycoprotein localized on the cell surfaces of myeloid cells, functions as a pattern recognition receptor for various bacterial products, such as LPS. Therefore, the aim of the present study was to determine whether the SNP at position -159 in the promoter region of the CD14 gene is associated with periodontal disease status in a Chinese Han population.

Material and method :A toatal of 270 subjects with CP(N=122), AgP(N=84), and periodontal health(N=64) volunteered to participate. Data concerning smoking, drinking and betal quid chewing were obtained by interviewing the subjects in association with the clinical examination. Genomic DNA was extracted from blood. Genotypes of CD14 -159 C/T were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The data were analyzed by χ2 test, one-way ANOVA and multiple logistic regression analyses. The risk for periodontitis associated with genotypes was calculated as the odds ratio (OR).

Result : The genotype distribution of CP patients showed that 13.9% were CC, 53.3% were CT, and 32.8% were TT. AgP patients showed that 11.9% were CC, 47.6% were CT, and 40.5% were TT. These were not significantly different from the distribution in control subjects(15.6% were CC, 42.2% were CT, and 42.2% were TT). Adjusted variables such as sex, age, smoking, drinking, and betal quid chewing, the prevalence of the CT+CC genotype compared with the TT genotypes was significantly lower in CP of non-smoking group. (Adj. OR: 0.41, 95% CI : 0.16 ~ 0.98)

Conclusion: The results of this study suggested that the TT genotype of the CD14 -159 C/T polymorphism seems to be associated with an increased risk for chronic periodontitis in a Taiwanese population. The TT genotype effect was overwhelmed by smoking habit.Further research is necessary to prove the polymorphisms to have a functional effect.

並列關鍵字

CD14 ； gene polymorphisms ； chronic periodontitis ； aggressive periodontitis

參考文獻

1. Madianos PN, Bobetsis YA, Kinane DF. Generation of inflammatory stimuli: how bacteria set up inflammatory responses in the gingiva. J Clin Periodontol 2005; 32 Suppl 6: 57-71.

2. Offenbacher S. Periodontal diseases: pathogenesis. Ann Periodontol 1996; 1: 821-78.

3. Offenbacher S, Heasman PA, Collins JG. Modulation of host PGE2 secretion as a determinant of periodontal disease expression. J Periodontol 1993; 64: 432-44.

4. Kinane DF, Shiba H, Hart TC. The genetic basis of periodontitis. Periodontol 2000 2005; 39: 91-117.

5. Yoshie H, Kobayashi T, Tai H, Galicia JC. The role of genetic polymorphisms in periodontitis. Periodontol 2000 2007; 43: 102-32.