高度糖化終產物受器基因多型性與 sRAGE，慢性牙周炎分別在非糖尿病與糖尿病台灣人之相關性

The association between the RAGE polymorphisms, sRAGE and chronic periodontitis in Taiwanese individuals with and without diabetes

吳泰練(Tai-Lien Wu)

指導教授 ： 林英助

高雄醫學大學/口腔醫學院/牙醫學系博士班/博士(2015年)

https://doi.org/10.6832/KMU.2015.00002

摘要

研究目的：探討高度糖化終產物接受器 (receptor for advanced glycation end products，RAGE) G82S、-374 T/A、-429 T/C 基因多型性 對慢性牙周炎易感受性，並進一步探討分層分析在糖尿病患者和非糖尿病族群之 RAGE 基因多型性對慢性牙周炎易感受性。另外也討論 RAGE 基因多型性與血液中 sRAGE 之相關性與 sRAGE表現量是否影響與慢性牙周炎有關。
材料與方法：研究對象分為慢性牙周炎組 (n=350) 與非牙周炎組 (n=118)，其中 260人非糖尿病，208 人為第二型糖尿病患者。所有調查對象可細分為慢性牙周炎非糖尿病組、慢性牙周炎糖尿病組、非牙周炎非糖尿病組、非牙周炎糖尿病組。以聚合酵素連鎖反應與限制酵素切割技術測定基因型。各基因型之分佈是否在組間分佈有差異是採用卡方檢定，各基因型與疾病危險之相關性是以邏輯式回歸分析，以 odds ratio 及 95%信賴區間表示。血液中 sRAGE 以 ELISA 方法檢測。各基因型與 sRAGE 的關係是以 ANOVA 分析。
結果：研究調查發現，在非糖尿病組，RAGE G82S 基因型分佈在慢性牙周炎組與非牙周炎對照組間具有顯著的差異(χ2=4.6，p=0.04)，在非糖尿病組進一步調整年齡、性別及吸菸狀態等變數後，G82S 基因多型性與慢性牙周炎其相關性依然存在 (GS+SS vs. GG，adjusted OR=2.03，95%CI = 1.07-4.00)。然而在糖尿病分組，G82S 基因型分佈在慢性牙周炎組與非牙周炎組間不具有統計上的差異。無論在總研究對象、非糖尿病組、糖尿病組， RAGE -429T/C 與 -374T/A 基因多型性與慢性牙周炎之間沒達統計上顯著相關，再進一步調整年齡、吸菸狀況、BMI 等可能造成的干擾後因素，仍沒達統計上顯著相關。在sRAGE部分，無論在總研究對象、非糖尿病組、糖尿病組血液中 sRAGE 濃度均與慢性牙周炎無關，在 G82S 基因多型性與血液中 sRAGE 濃度的相關性分析結果顯示，研究對象攜帶 G82G 基因型相對於 G82S+S82S 基因型在非糖尿病 (857.0 ± 333.4 vs. 728.5 ± 312.5 pg/ml，p< 0.0001) 與糖尿病 (901.9 ± 500.8 vs. 616.5 ± 301.9 pg/ml， p < 0.0001) 均有較低的血液 sRAGE， -429T/C 與 -374T/A 基因多型性則均與血液中 sRAGE 濃度沒有相關，在研究對象攜帶 G82S+S82S 基因型中，可見糖尿病組血中 sRAGE 的量相較於非糖尿病組是有顯著較低 (616.5 ± 301.9 vs. 728.5 ± 312.5 pg/ml，p<0.03)。
結論：非糖尿病族群的 G82S 基因多型性可能與慢性牙周炎的發生有關。但是在糖尿病患者 G82S 基因多型性與慢性牙周炎的發生無明顯相關。血液中sRAGE 濃度與慢性牙周炎無關，血液中 sRAGE 濃度表現與 G82S 基因多型性有關。

關鍵字

RAGE ； 慢性牙周炎 ； 基因多型性 ； 糖尿病

並列摘要

Background and Objective: The present study investigated the association between the RAGE G82S、-374 T/A、-429 T/C polymorphisms, the plasma levels of sRAGE and chronic periodontitis (CP) in subjects with and without diabetes mellitus (DM).
Material and Methods: A total of 208 DM patients and 260 non-DM participants were recruited for this study. Genotyping of the RAGE G82S、-374 T/A、-429 T/C polymorphisms were accomplished using PCR-RFLP, and associations were analyzed with the chi-square test and logistic regression analysis.
Results: In the non-DM group, the chi-square test showed that the frequency distributions of the G82S polymorphisms were significantly different between CP and non-CP subjects (χ2 = 4.6, p = 0.04). A multivariate logistic regression model showed that the G82S+S82S genotypes were associated with a significantly increased risk of CP development compared to the G82G genotype (adjusted odds ratio (OR) = 2.03, 95% confidence interval (CI): 1.07- 4.00). In the DM group, there was no association between the G82S polymorphism and CP development when a multivariate logistic regression was performed. In total, non-DM and DM group, there were no association between the RAGE -374 T/A、-429 T/C polymorphisms and CP development when a multivariate logistic regression was performed. There was no difference in plasma sRAGE levels between CP and non-CP subjects in total, DM and non-DM groups. Plasma levels of sRAGE were significantly higher in subjects with the G82G genotype compared to those with the G82S +S82S genotypes in both the non-DM (857.0 ± 333.4 vs. 728.5 ± 312.5 pg/ml, p< 0.0001) and DM groups (901.9 ± 500.8 vs. 616.5 ± 301.9 pg/ml, p < 0.0001). There were no association between -429 T/C、 -374 T/A polymorphisms and plasma sRAGE levels. Plasma levels of sRAGE were significantly lower in DM group compared to non-DM group in subjects with the G82S+S82S genotypes (616.5 ± 301.9 vs. 728.5 ± 312.5 pg/ml，p<0.03).
Conclusions: The present study revealed that the RAGE G82S polymorphism was associated with chronic periodontitis in the non-DM group but not in the DM group. Our results also showed that the plasma levels of sRAGE were significantly higher in subjects with the RAGE G82G genotype, and this correlation was not affected by the presence of CP in the DM and non DM groups.

並列關鍵字

RAGE ； chronic periodontitis gene ； polymorphisms ； diabetes mellitus

參考文獻

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