嚴崇仁2006-07-262018-07-112006-07-262018-07-112004http://ntur.lib.ntu.edu.tw//handle/246246/23612自由基（free radicals ）會破壞體內的大分子物質，可能和糖尿病之長期併發症有 關。有一些研究顯示：粒腺體內染色體的突變與某些人罹患糖尿病有關。第二型超氧 化物歧化酵素（或Mn-superoxide dismutase, Mn-SOD ）是由體染色體控制而在粒腺體 內代謝自由基的酵素之一，若此酵素之基因有突變存在，可能會導致自由基代謝速率 改變，使粒腺體內染色體或蛋白質受自由基攻擊的機會上升，而使某些人容易罹患糖 尿病。因此吾人將探討Mn-SOD 基因是否為糖尿病或其併發症的候選基因（candidate gene ）。近來的研究發現Mn-SOD 的粒腺體導引序列（mitochondrial targeting sequence ） 有Ala-9Val （鹼基由T 變成C ）多型性存在，此多型性變化可能會導致Mn-SOD 無法 正確輸送至粒腺體代謝自由基。為了評估此多型性變化之臨床意義，吾人進行此實驗。 首先我們收集健康志願者（共收集到27 位基因型為CT 、77 位為TT 者），取其 白血球來觀察白血球在高糖(25mM)狀態下釋放chemiluminescence （或氧化壓力）是否 受基因型之影響；結果CT 、TT 兩組沒有明顯差異。其次，我們收集4 組受試者，包 括：309 位健康志願者、248 位非糖尿病末期腎病患者、57 位糖尿病無明顯併發症者 以及114 糖尿病併末期腎病患者，統計發現CC 、CT 、TT 基因型在各組之分佈亦無明 顯差異。因此Mn-SOD 基因之Ala-9Val 多型性可能不會增加發生糖尿病或糖尿病腎病 變之危險性。Free radicals can attack macromolecules in the body and may contribute to the development of long-term complications of diabetes mellitus. Several reports have shown that mutations of mitochondrial DNA are associated with the susceptibility of diabetes mellitus. Type II superoxide dismutase or Mn-superoxide dismutase (Mn-SOD) is encoded in nuclear DNA and it is, then, sent into mitochondria for metabolizing superoxide. If there is an Mn-SOD gene mutation, the metabolism of free radicals may change and the risk of mitochondrial DNA and proteins damage by free radicals may increase, which may lead to increased susceptibility to diabetes mellitus. Therefore, Mn-SOD gene may be a potential candidate gene for diabetes mellitus and its complications. Previous studies had found an Ala-9Val polymorphism (T to C change in nucleotide) in the mitochondrial targeting sequence of human Mn-SOD. The polymorphism may affect its effective transport to mitochondria and ability to metabolize free radicals. To determine the clinical significance of the polymorphism, we performed this study. We first recruited 104 healthy volunteers with different genotypes (27 CT and 77 TT cases) to observe the difference of chemiluminescence released from leukocytes in high glucose state (25mM). There was no statistical difference in chemiluminescence (or oxidative stress) between the CT and TT group. Then, another 4 groups of volunteers were enrolled, including 309 normal controls, 248 nondiabetic uremic subjects, 57 diabetics without apparent complications and 114 patients of diabetic nephropathy in end-stage renal disease. The distribution of CC/CT and TT genotypes was not statistically different among the 4 groups. Therefore, Ala-9Val polymorphism in Mn-SOD gene probably does not contribute to the increased susceptibility of diabetes or diabetic nephropathy.application/pdf41154 bytesapplication/pdfzh-TW國立臺灣大學醫學院內科過氧化物歧化酵素基因糖尿病粒腺體superoxide dismutasediabetes mellitusmitochondria[SDGs]SDG3reporthttp://ntur.lib.ntu.edu.tw/bitstream/246246/23612/1/912314B002346.pdf