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  • 學位論文

Sulfonylurea receptor 1及Kir6.2的基因多型性與第二型糖尿病患者給藥治療影響性分析

The association of Sulfonylurea receptor 1 and Kir6.2 gene polymorphism with the treatment of Sulfonylurea and Biguanide in the type 2 diabetes mellitus patients

指導教授 : 吳信昇
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摘要


本研究是探討服用磺基尿素類(Sulfonylureas)或雙胍類(Biguanide)降血糖藥之糖尿病患者其藥效與Sulfonylurea receptor及Kir6.2基因多型性的影響性分析,應用的方法:利用聚合酵素鏈鎖反應與限制酶切割片段長度多型性等技術進行病人不同基因的多型性分析,經由不同的基因多型性分析配合不同的藥物處理,再經由統計分析的結果可以獲得藥物與不同基因多型性的關係。 符合本研究之研究對象共116人,皆為第二型糖尿病患者,ABCC8-E16單一核苷酸多型性(Single nucleotide polymorphism, SNP)的基因型分佈為:CC基因型有9位(7.7%),CT基因型有45位(38.5%),TT基因型有62位(53.8%),KCNJ11-E23K SNP的基因型分佈(genotype distribution):GG基因型有2位(1.7%),GA基因型有6位(5.2%),AA基因型有108位(93.1%),且ABCC8-E16 TT基因型與KCNJ11-E23K AA基因型表現在第二型糖尿病患者的頻率較高,且亦為罹患第二型糖尿病的危險因子。 利用Oneway ANOVA分析,得知分析ABCC8-E16與KCNJ11-E23K基因多型性與糖尿病藥物治療之影響分析,其結果分別為: ABCC8-E16 TT基因型的病患適合給予Sulfonylurea類降血糖藥物治療(P<0.05),KCNJ11-E23K基因多型性與Sulfonylurea類降血糖藥物治療則無顯著關係,可將此結果提供臨床醫師作為糖尿病藥物治療的參考依據,進而能有效控制血糖,減少併發症之發生,改善病患之生活品質。

並列摘要


We analysed the association of Sulfonylurea receptor and Kir6.2 gene polymorphism with the treatment of Sulfonylureas or Biguanide in the diabetics. We utilize method include the Polymerase chain reaction (PCR) and Restriction fragment length polymorphism (RFLP) etc., for proceeding analysis gene polymorphism in all patients. Besides, the purpose of the study is to understand the relationship between gene polymorphism and antidiabetic treatment in statistics analysis. Subjects with type 2 diabetes mellitus(n=116) were randomly selected from Kaohsiung Armed Force General Hospital. The genotype distribution of E16 was: 7.7% for the CC genotype (n=9), 38.5% for CT genotype (n=45), 53.8% for TT genotype (n=62), and the genotype distribution of exon 23k was:1.7% for GG genotype (n=2), 5.2% for GA genotype (n=6), 93.1% for AA genotype (n=108).The ABCC8 E16-TT and KCNJ11 E23K-AA genotype appeared at higher frequency in type 2 diabetic populations, that seem to confer a risk factor for developing type 2 diabetes. Oneway ANOVA was used to analysis antidiabetic treatment between ABCC8 and KCNJ11 polymorphism. In conclusion, we observed ABCC8-E16 TT genotype to reach significance statistic analysis for the sulfonylurea treatment (P<0.05), but no association between KCNJ11-E23K AA genotype and sulfonylurea treatment (P=0.08).The result could assist diagnosis and referral for prescribing to the type 2 diabetes, that also can improve patients diabetic control and quality of life.

參考文獻


1.American Diabetes Association. Hyperglycemic crises in
patients with diabetes mellitus. Diabetes Care. 2001; 24
(1): 154-161.
2.American Diabetes Association. Report of the expert
committee on the diagnosis and classification of diabetes mellitus. Diabetes Care 2001; 24 supp1: S5-S19.

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