透過您的圖書館登入
IP:54.210.83.20
  • 學位論文

趨化因子受體 CCR5的基因多型性和冠狀動脈疾病 在中台灣 – 一個單一醫學中心的研究

Genetic Polymorphism in the CC-chemokine receptor- 5(CCR5) gene and coronary artery disease in the central section of Taiwan- a single medical center study

指導教授 : 翁國昌 楊順發

摘要


研究背景 冠狀動脈疾病(coronary artery disease, CAD)已經成為現今各國所面臨的重要健康問題。在以往HIV的研究顯示,有CCR5 缺失的單核苷酸基因多型性之族群中,對於HIV具有阻抗性且有較少的心血管疾病。在目前的動物實驗中也證實了CCR5 和它的配位體CCL3(MIP-1α), CCL4(MIP-1β), and CCL5(RANTES),與粥狀動脈的發生和進展息息相關。在歐美的一些病例對照研究也發現此一類似的現象。然而,CCR5 和冠狀動脈疾病的關係在台灣的族群中尚未確立,本研究即探討 CCL5-403 和CCR5-59029 的單核苷酸基因多型性與心血管疾病的臨床表現。 材料與方法 我們共收納了483例因胸痛而安排心臟冠狀動脈血管攝影的病患,收案時間為西元2007年4月至2009年3月。病患收集的資料包括性別、 年齡、症狀、病史及生化檢查數值。根據冠狀動脈血管攝影檢查之結果,分成有冠狀動脈疾病組(病例組,n=322 人) 和無冠狀動脈疾病組(控制組,n=161 人),並採用聚合酶鏈反應-限制性片段長度多型性(PCR - RFLP)的方法,來分析兩組的臨床特性和CCL5-403、CCR5-59029的單核苷酸基因多型性之關係。 研究結果 CCL5 -403 的TT的基因型(genotype)頻率在病例組為9.9%,在控制組為3.7%,其odds ratio為3.063 (1.231~ 7.624),且具有統計學上之差異( p=0.012)。CCL5 -403 的T等位基因 (T allele) 的頻率在病例組為32% ,在控制組為25.5%,其odds ratio為 1.377 (1.019 ~1.859),且具統計學上之差異( p=0.037)。就Troponin-I 呈陽性的比例而言,CCR5- 59029(GA + AA)的基因型有66.3%,CCR5-59029 GG的基因型有51.5%,其odds ratio 為1.853 (1.176~ 2.921) 且具有統計學之差異(p=0.008)。 結論 對於CCL5-403的單核苷酸基因多型性而言,具有TT基因型的患者較易得冠狀動脈疾病,而具有T 等位基因的患者有較高的比例得冠 狀動脈疾病。對於CCR5-59029的單核苷酸基因多型性而言,具有GA+AA基因型的患者較易發生急性冠心症。本研究的 CCL5-403 和 CCR-5 59029的單核苷酸基因多型性或許可以成為genotype score 的一項因子,更進而預測心血管事件的機率。

並列摘要


Background: The importance of Coronary artery disease (CAD) in contemporary society is attested to by the almost epidemic number of persons afflicted. The chemockine receptor CCR5 was initially known for its role as a co-receptor for HIV infection. The CCR5 deletion polymorphism CCR5 delta32, which confers resistance to HIV infection, has been associated with reduced risk of cardiovascular disease. Additionally, evidence is now emerging supporting a role for CCR5 and its ligands CCL3(MIP-1α), CCL4(MIP-1β), and CCL5(RANTES) in the initiation and progression and progression of atherosclerosis. However, the association of CCR5 polymorphism and cardiovascular disease in Taiwanese was not confirmed. So, we investigated the single nucleotide polymorphism of chemokine receptor(CCR5-59029、CCL5-403) and the related clinical features. Materials and methods: We studied 483 unrelated patients(430 males and 9 females) receiving coronary angiography because of chest pain at Chung Shan Medical University Hospital. The patients were recruited from April 2007 to March 2009. The collected data included genders, age, symptoms, history and biochemical data. The blood sample was obtained for single nucleotide polymorphism study by PCR-RFLP assay. We assessed the demographic characteristics between case group(N=322 ) and control group(N=161). Additionally, the odds ratio analysis of CCR5-59029 and CCL5-403 single nucleotide polymorphism was performed by genotype and allel. Results: CCL5-403 with TT genotype frequencies were different in CAD group and non-CAD group (9.9 % vs 3.7%, odds ratio=3.063, p=0.012). CCL5-403 polymorphism with T allele was higher in CAD group (32.0 % vs 25.5%, odds ratio=1.377, p=0.037). CCR5-59029 with GA+AA genotype was associated with increased acute coronary syndrome prevalence(66.3% vs 51.5%, odds ration=1.853, p=0.008) Conclusion: In our study, CCL5-403 polymorphism may increase genetic susceptibility of CAD. TT genotype or T allele were associated with CAD. CCR5-59029 with GA+AA genotype could increase the prevalence of ACS. CCL5-403 or CCR-5 59029 single nucleotide polymorphism may include genotype score and it may predict cardiovascular event.

參考文獻


56. Sharda S, Gilmour A, Harris V, Singh VP, Sinha N, Tewari S et al.
63. Mary Fran Hazinski and David Gilmore(2008). Handbook of emergency cardiovascular care. American heart association
41. Hyde CL, MacInnes A, Sanders FA, Thompson JF, Mazzarella RA,
39. Papaspyridonos M, Smith A, Burnand KG, Taylor P, Padayachee S,
42. Dol F, Martin G, Staels B, Mares AM, Cazaubon C, Nisato D et al.

延伸閱讀