Interleukin-6基因多型性與糖尿病、牙周疾病之相關性探討

The relationship between Interleukin-6 gene polymorphism and Diabetes mellitus、 periodontal disease

張鈞智(Chun-Chih Chang)

指導教授 ： 蔡吉政

高雄醫學大學/口腔醫學院/口腔衛生科學研究所碩士班/碩士(2008年)

https://doi.org/10.6832/KMU.2008.00144

摘要

研究目的：糖尿病與牙周病的關係已經討論了許久，大部分的流行病學發現糖尿病患者有比較高的牙周疾病盛行率及牙周破壞程度，此外糖尿病患者的血糖控制也與牙周疾病的發生有關；牙周病影響糖尿病方面，觀察到許多糖尿病患者有嚴重牙周病時，其血糖控制顯著的較差的情形；糖尿病與牙周疾病是慢性發炎的多基因參與的免疫系統疾病，因此慢性發炎物IL-6被認為在兩者的關係間扮演著重要的角色。IL-6 -572基因多型性為IL-6最常被探討到的SNP之ㄧ，其引子上的基因轉錄活性與其濃度有明顯的關係存在。本研究將探討IL-6 -572基因多型性與血清中IL-6濃度與糖尿病、牙周狀態之關係。

研究設計與方法：本研究共收案191位糖尿病病患與216位非糖尿病族群，並針對兩組群做口腔檢查(CPI、PI)與相關資料的收集。採用PCR-RFLP的方式判斷兩組群的IL-6 -572基因多型性；IL-6之血清濃度則以ELISA方式測定。研究結果以統計軟體JMP 6.0進行雙樣本t檢定、卡方檢定、邏輯式廻歸分析。(分析中CPI≦2定義為非牙周病組，CPI＞2為牙周病組；血糖控制HbA1c≦7定義為血糖控制好，HbA1c＞7為血糖控制不好)。

結果：IL-6基因型與血清中IL-6濃度的關係並無統計上意義，僅觀察到CC基因型、C allele有比較高的濃度。IL-6的濃度在各組群的比較中也沒有發現差異存在，但不管在糖尿病與非糖尿病的牙周病組群中IL-6的濃度都有比較高的趨勢。IL-6與牙周病關係方面，在糖尿病組群IL-6 CC基因型與牙周疾病的易感受性有關，CC基因型得到牙周疾病的危險性為CG＋GG基因型的2.12倍。抽菸是牙周疾病的危險因子，分層分析後發現糖尿病沒有抽菸的組群CC基因型得到牙周疾病的機率為CG與GG的2.33倍，非糖尿病組群沒抽菸組群並沒有觀察到基因型與牙周疾病的關係存在。此外，不同血糖控制情況下的基因型與牙周疾病關係的分析中，發現血糖控制好的組群，IL-6基因型與牙周疾病的易感受性無關;血糖控制不好的族群IL-6 CC基因型得到牙周疾病的機率為CG＋GG的2.96倍。

結論：IL-6 -572基因型與糖尿病人血糖控制不好族群的牙周病發生易感受性有關，CC基因型在糖尿病人牙周病發展上扮演著重要的角色。

關鍵字

糖尿病 ； 牙周病 ； 血糖控制 ； 介白質-6(interleukin-6)

並列摘要

Objective: The relationship between diabetes and periodontal disease has been long discussed. Numerous epidemiology studies found that diabetes patients had high a higher prevalence of severe periodontitis than those without diabetes; those with poor glycemic control diabetes had highest prevalence. Both of these diseases are polygenic disorder and related with chronic inflammation. Interleukin-6 is one of the proinflammatory cytokins, which have been reported associated with diabetes and periodontal disease, respectively. It seems that IL-6 may play an important role in periodontitis and diabetes mellitus. In this study, we investigated the relationships among IL-6 gene polymorphism (-572), IL-6 level of plasma, periodontal status and glycermic control parameters in non-diabetes and diabetic patients

Methods: We recruited 206 subjects without diabetes and 191 diabetes patients. All subjects had at least 20 or more teeth. Community periodontal index (CPI) and plaque index (PLI) were examined by trained dentists and IL-6 polymorphism and IL-6 level of plasma were determined by PCR-RFLP analysis and enzyme-linked immunoabsorbent assay respectively.

Results: The frequency of the -572C/C genotype was significantly associated with periodontitis (P=0.03). The odds ratio(OR) for periodontitis was 2.12 with 95%CI of 1.07-4.25 for diabetic patients of CC genotype compared with those of CG or GG genotype. However, there was no associated between periondotitis and IL-6 gene polymorphism in non-diabetic groups when exclude the confounding factor: tobacco smoking. Among diabetes group those with HbA1c＞7%, the OR increased to 2.96 with 95%CI of 1.19-2.96. There were no significant association between IL-6 level of plasma periodontitis, blood glucose control status and IL-6 genotype.

Conclusion: IL-6 gene polymorphism was associated with susceptibility to chronic periodontitis in a population of Taiwanese diabetic patients. In diabetic patients with poor glycemic control, those with CC genotype may have a higher risk for susceptibility to periodontitis than those with CG or GG genotype.

並列關鍵字

Diabetes ； periodontitis ； glycemic control ； IL-6(interleukin-6)

參考文獻

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