CYP1A1 MspI 及GST M1基因多型性與眼翳發生的關聯

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Title:	CYP1A1 MspI 及GST M1基因多型性與眼翳發生的關聯 Association between the risk of pterygium and genetic polymorphism in CYP1A1 MspI and GST M1 genes
Authors:	羅育倫;Yu-Lun Lo
Contributors:	醫學院臨床醫學研究所碩士班
Keywords:	眼翳;細胞色素P450 1A1;麩胺硫轉移酵素M1;多型性;多環芳香烴;苯並芘;BPDE;pterygium;CYP1A1;GST M1;polymorphism;PAH;BaP;BPDE
Date:	2010
Issue Date:	2010-09-29 12:16:45 (UTC+8)
Abstract:	研究目的研究細胞色素P450 1A1基因(CYP1A1)及麩胺硫轉移酵素M1基因(GST M1)多型性與眼翳(pterygium)發生的關聯。細胞色素P450 1A1及麩胺硫轉移酵素M1都是參與多環芳香烴化合物(PAH)代謝的酵素，BaP 7,8-diol 9,10-epoxide (BPDE) 是多環芳香烴化合物苯並芘(BaP)中極具生物活性的中間代謝產物，會攻擊 DNA形成 BPDE-DNA共價鍵結物並導致 p53基因的突變，之前的研究指出，眼翳組之中 BPDE-like DNA共價鍵結物含量與 CYP1A1基因多型性有顯著的關聯性，因此本研究進一步研究 CYP1A1及 GST M1基因多型性與眼翳發生的關聯。研究方法本研究共收集了205個眼翳切片組織與206個正常對照週邊血液檢體，將檢體DNA經由純化萃取，先以聚合酶連鎖反應將標的片段放大，再利用限制酶片段多型性的方法，以電泳決定 CYP1A1與 GST M1基因的多型性，並進一步統計分析 CYP1A1與 GST M1的基因型多型性在眼翳組織與正常對照組間的差異。研究結果本研究發現 CYP1A1基因多型性的分佈在眼翳組織與正常對照組間有顯著的差異(p=0.017)，但在 GST M1基因多型性的分佈在兩組間並沒有發現有顯著的差異(p=0.952). CYP1A1 T/C變異型發生眼翳狀贅的機會是野生型T/T的1.372倍(勝算比1.372，95% 信賴區間=0.906-2.079, p=0.135)，CYP1A1 C/C變異型發生眼翳狀贅的機會是野生型T/T的2.711倍(勝算比2.711，95% 信賴區間=1.331-5.524, p=0.006)，而GST M1基因的變異型比起野生型並沒有統計上顯著增加的勝算比。研究結論 CYP1A1基因的多型性與眼翳發生有顯著的關聯，CYP1A1基因的多型性或許可成為預測眼翳發生的預測因子，此外，依此研究我們推論除了紫外線暴露外，環境中的污染物質也可能是眼翳發生的影響原因之ㄧ。 Purpose: To study the association between the risk of pterygium and genetic polymorphism in cytochrome P450 1A1 (CYP1A1) and glutathione S-transferase Mu1 (GST M1). Both CYP1A1 and GST M1 have been demonstrated to be involved in the metabolism of polycyclic aromatic hydrocarbons (PAHs). BaP 7,8-diol 9,10-epoxide (BPDE), an ultimate metabolite of benzo(a)pyrene (BaP), attacks deoxyguanosine to form a BPDE-N2-dG adduct resulting in p53 mutations. Our previous report indicated that BPDE-like DNA adduct levels in pterygium was associated with CYP1A1 gene polymorphisms. Therefore, we hypothesize that the genetic polymorphisms of CYP1A1 and GST M1 increase the risk for pterygium. Methods: 205 pterygial specimens and 206 normal controls were collected in this study. For the analysis of CYP1A1 and GST M1 gene polymorphisms, DNA samples were extracted from pterygium specimens and blood cells of normal controls respectively and then subjected to polymerase chain reaction and restriction fragment length polymorphism for the determination of mutation and genotype of the CYP1A1 and GST M1 genes. Results: There was a significant difference between the case and control groups in the CYP1A1 MspI genotype (p=0.017) but not in GST M1 (p=0.952). The odds ratio of the CYP1A1 T/C genotype polymorphism was 1.372 (95% CI=0.906-2.079, p=0.135) and the C/C genotype polymorphism was 2.711 (95% CI=1.331-5.524, p=0.006), compared to the T/T wild-type genotype. The GST M1 polymorphisms did not have an increased odds ratio compared with the wild type. Conclusion: In conclusion, CYP1A1 polymorphism is correlated with pterygium and might become a marker for the prediction of pterygium susceptibility. According to this research, we may further infer that the environmental pollution may also play a role in the pathogenesis of pterygium formation.
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