研究背景
自血管張力素轉換?2(angiotensin converting enzyme 2, ACE2)於二○○○年被發現以來，其於腎素-血管張力素系統(Renin-angiotensin system, RAS)內的角色逐漸被確認，可引發下游血管擴張、抗發炎、抗細胞增生等機轉，故被認為有心血管疾病的保護作用。近年來的研究發現ACE2基因的多型性可能會影響心血管疾病的易感性。本研究希望分析台灣人的ACE2基因多型性的分佈情形，並分析其是否與冠狀動脈心臟病(coronary artery disease)之易感性有關聯。
研究方法
從受試者的週邊血液中抽取DNA進行即時定量聚合?連鎖反應(Quantitative real-time PCR) ，分析ACE2基因於rs2285666、rs4646142、rs2106809及rs4240157四個位點的單一核?酸多型性(single-nucleotide polymorphism) ，並比較冠狀動脈心臟病組和對照組二組間基因型的差異。因ACE2基因位於X染色體上，故分析結果需將男女生分開探討。
研究結果
本研究共收納了379位冠狀動脈心臟病組(冠心病組)和205位對照組共584位受試者，統計分析發現二組在ACE2基因四個位點的基因多型性的分佈上，不論男女，均沒有顯著差異。僅可見在女性rs2285666的T/T型、rs4646142的G/G型及rs2106809的A/A型分佈傾向於對照組，但均無達到統計意義。
結論
本研究發現ACE2基因上rs2285666、rs4646142、rs2106809及rs4240157的單一核?酸多型性，並不影響冠狀動脈心臟病的易感性，這可能與族群差異、樣本數或是樣本選擇偏差有關。ACE2基因多型性與冠狀動脈心臟病的關係需要更多的研究與探討。
Background Angiotensin-converting enzymes 2 (ACE2) was discovered in year 2000 by two independent groups. Its major role is to degrade angiotensin II to the heptapeptide Ang-(1-7) within the renin-angiotensin system. It may limit the vasoconstrictor action of angiotensin II through its inactivation, as well as counteracting the actions of angiotensin II through the formation of Ang-(1-7), which is reported to have vasodilatory, anti-fibrotic and anti-proliferative actions. Thus, it is considered as having cardioprotective effects. Recent studies found that genetic polymorphisms of ACE2 gene may have association with coronary artery disease. We want to evaluate the distribution of genetic polymorphisms of ACE2 gene of Taiwanese people and its relationship with coronary artery disease susceptibility. Method Genomic DNA was extracted from peripheral blood samples and the allelic discrimination of ACE2 rs2285666, rs4646142, rs2106809 and rs4240157 was assessed using quantitative real-time PCR method. The genetic distribution of these positions and the association with coronary artery disease were statistically analyzed. The results were discussed separately for men and women as the ACE2 gene is located on X chromosome. Results A total of 584 Taiwanese patients were recruited and analyzed in this study. There were 379 patients in CAD group (276 male and 103 female) and 205 in control group (119 male and 86 female). Statistical analysis revealed no significant differences in the genetic distribution of these four ACE2 single nucleotide polymorphisms between CAD group and control group in men and women. There is only a trend that the rs2285666 T/T genotype, rs4646142 G/G genotype and rs2106809 A/A genotype were more in the control group. Conclusion Some study found that there was association between ACE2 single nucleotide polymorphisms and coronary artery disease. Our data suggests that there is no relationship between these four ACE2 single nucleotide polymorphisms and coronary artery disease susceptibility. It may be due to ethnic difference, sample size or selection bias. Further studies are needed to clarify the potential role of ACE2 single nucleotide polymorphisms in the coronary artery disease continuum.
