*中心館藏網址:http://tulips.ntu.edu.tw/record=b2173957*cht  

[ 摘要 ]
一氧化氮在人體中扮演多重角色，對血壓的調節十分重要，可以使血管平滑肌舒張，抑制血小板和單核白血球在血管壁上的凝集，並可抑制血管平滑肌細胞的增生。一氧化氮分泌量過少，會造成各種心血管疾病，例如使人容易罹患高血壓、血栓症、動脈痙攣、冠狀動脈疾病，和動脈粥樣硬化…等心血管疾病。反之，分泌量過多，過多的自由基更是會毒害細胞、組織及器官。一氧化氮合成酶為生物體內合成一氧化氮所必須的酵素。人類一氧化氮合成酶基因的多型態（polymorphism）會影響一氧化氮合成酶表現或活性，造成人體中一氧化氮分泌量的不差異，以及罹患心血管疾病罹患率的差異。國外的文獻顯示，基因頻率和基因型與疾病的關係在各族群的研究上差異頗大；目前國內並這方面的研究報告並不多見。因此本實驗選取經花蓮慈濟醫院診斷確定之心血管疾病患者120人為心血管疾病組與急診之非心血管疾病患者45人為非心血管疾病組以及37名無心血管疾病之卑南族為卑南族組，利用聚合酶鏈反應（polymerase chain reaction, PCR）檢測一氧化氮合成酶在 intron 4，27 bp repeat polymorphism，和在exon 7 G894T polymorphism (Glu298Asp)；目的在於建立台灣東部一氧化氮合成酶4b/a與G894T基因型的頻率，以及探討其與心血管疾病的罹患是否相關。實驗結果顯示，一氧化氮合成酶在 intron 4，27 bp 重複序列基因型在心血管疾病組（aa：ab：bb=3.33%：21.67%：75.00%）、非心血管疾病組（aa：ab：bb=0%：17.07%：82.93%）、卑南族組（aa：ab：bb=0%：27.03%：72.97%）之間的頻率分佈相似。心血管疾病組和非心血管疾病組相比，P=0.38；卑南族組和非心血管疾病組相比，P=0.29。因此無法證明一氧化氮合成酶基因在 intron 4，27 bp 重複序列多型態與心血管疾病的相關性。一氧化氮合成酶基因在exon 7 G894T的多型態，在心血管疾病組（TT：GT：GG=5.36%：74.11%：20.54%）、非心血管疾病組（TT：GT：GG=6.67%：22.22%：71.11%）和卑南族組別（TT：GT：GG=8.11%：37.84%：54.05%）的分佈有顯著差異；心血管疾病組和非心血管疾病組相比，P<0.001；卑南族組和非心血管疾病組相比，P=0.262；卑南族組和心血管疾病組相比，P<0.001。一氧化氮合成酶基因在exon 7 G894T的多型態，在這次的實驗中顯示可能是引發心血管疾病的危險遺傳因子之一。

[ 英文摘要 ]
Nitric oxide (NO) is one of the most versatile molecules in the biological system. It acts as a trigger, mediator, or effector to many biological reactions and signal transductions. NO plays an important role in the regulation of blood pressure, and vascular tone. It causes vasodilatation by relaxation of the vascular smooth muscle and vasodilatation, mediates shear-induced endothelial cell-dependent vasodilatation, and inhibits vascular smooth muscle cell proliferation and monocyte and platelet adhesion. Endothelial constitutive nitric oxide synthase is the key enzyme in determining basal NO production in vascular beds. Preview studies have showed an association between the alleles of the ecNOS gene polymorphism and the plasma NO metabolite levels in humans. Reduction in basal NO release may predispose humans to cardiovascular diseases, including hypertension, coronary arterial disease, and atherosclerosis. Conversely, overproduction of nitric oxide can cause peroxynitrite accumulation leading to damage of cells, tissue, and organs. Many investigations have found that some variants of endothelial constitutive nitric oxide synthase (ecNOS) gene vary in different ethnic populations. However, few studies with respect to variants of ecNOS gene polymorphism had been conduct in Taiwan. To explore the relationships between ecNOS gene polymorphism and cardiovascular disease in eastern Taiwan, all diagnosed patients and control subjects without history of cardiovascular disease will be collected from hospital. The polymorphism will be analyzed by polymerase chain reaction. The study of the 27 bp repeat polymorphism in intron 4 had showed the frequencies of ecNOS genotype were similar for patients (aa: ab: bb=3.33%: 21.67%: 75.00%), controls (aa: ab: bb=0%: 17.07%: 82.93%), and Puyuma group (aa: ab: bb=0%: 27.03%: 72.97%). There is no evidence of an association between the 27 bp repeat polymorphism of the ecNOS gene and cardiovascular diseases (P>0.05). The frequencies of the Glu298Asp variant (G894T) of the ecNOS gene were different for patients (TT: GT: GG=5.36%: 74.11%: 20.54%), Puyuma group (TT: GT: GG=8.11%: 37.84%: 54.05%), and controls (controls, TT: GT: GG=6.67%: 22.22%: 71.11%). In this study, the Glu298Asp variant (G894T) of the ecNOS gene appeared to be a genetic risk factor of cardiovascular diseases.