探討第二型二甲基精胺酸二甲胺水解酶的基因多型性和台灣民眾的冠狀動脈疾病易敏感性的關係

Association of dimethylarginine dimethylaminohydrolase-2 gene polymorphism and the susceptibility of coronary heart disease in Taiwanese population

黃宏凱(Hung-Kai Huang)

指導教授 ： 翁國昌

中山醫學大學/醫學院/醫學研究所/碩士(2013年)

https://doi.org/10.6834/CSMU.2013.00036

摘要

冠狀動脈性心臟病為世界性的人口死亡的主要原因之一，的發生是和冠狀動脈的粥狀動脈硬化有關。一氧化氮被稱為抗動脈硬化分子，因為有經內皮細胞所作用的血管擴張能力和抑制血小板凝集能力。內生性的一氧化氮抑制劑，非對稱性二甲基精胺酸，是生成一氧化氮後的產物。非對稱性二甲基精胺酸目前被認為是冠狀動脈性的心臟病的危險因子。第二型二甲基精胺酸二甲胺水解酶主要展現在血管內皮細胞之中，是主要在血管內皮細胞內分解非對稱性二甲基精胺酸。本研究的目的是要探討第二型二甲基精胺酸二甲胺水解酶的基因多型性和台灣民眾的冠狀動脈性心臟病的易敏感性的關係。本研究是case-control study，包含了337位有冠狀動脈性心臟病的病人和147位沒有冠狀動脈心臟病的受試者。所有病人都分析其在rs805305和rs2272592的基因多型性的位置的基因型。基因型的測定是採用即時定量的聚合酶鏈式反應。在有冠狀動脈性心臟病的病人和沒有冠狀動脈性心臟病的受者之間，兩個被研究的基因多型性的位置的基因型的分佈頻率是沒有統計學上的差異性。在有冠狀動脈性心臟病的這一個族群的分析發現在rs805305位置帶有原始型(G/G)比帶有改變的核酸甘的基因型(G/C和C/C)有較高的比率有心臟酵素上升。所以推測在台灣冠狀動脈性心臟病的病人在rs805305位置帶有C的核苷酸可能是一個有保護免於心肌受傷的基因標誌。

關鍵字

冠狀動脈性心臟病 ； 第二型二甲基精胺酸二甲胺水解酶基因多型性

並列摘要

Coronary heart disease (CHD) is a leading cause of death worldwide and is originated from atherosclerosis of coronary artery. The nitric oxide is called anti-atherogenic molecule and is considered to induce endothelium-dependant vasodilatation and inhibit platelet aggregation. Endogenous nitric oxide inhibitor, asymmetric dimethylarginine, is metabolites of nitric oxide and is certified as risk factor of coronary heart disease. The dimethylarginine dimethylaminohydrolase 2, majorly expressed in the endothelium, is the key enzyme degrading the asymmetric dimethylarginine in the human body. The arm of the presenting study was to assess the association between the DDAH-2 gene polymorphism and coronary heart disease in Han population in Taiwan. We used case-control study including 337 CHD patients and 147 control subjects. All CHD patients and controls were genotyped for the same two single nucleotide polymorphisms (SNP) (rs805305 and rs2272592) of DDAH2 promoter gene by a real-time PCR instrument. There was no distribution difference of these two polymorphic loci between CHD patients and control subjects. In the CHD group, patients with wild-type genotype (G/G) at rs805305 had significantly more percentage to have elevated cardiac enzyme than those with altered-nucleotide genotype (G/C and C/C). The carriage of C allele at rs805305 could be a protective genetic maker from elevated cardiac enzyme in patients with CHD.

並列關鍵字

Coronary heart disease ； DDAH-2 ； single nucleotide polymorphism

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