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  • 學位論文

血小板衍生生長因子C基因多形性與缺血性中風之相關性研究

Association of the platelet-derived growth factor C genetic polymorphisms with ischemic stroke

指導教授 : 邱弘毅

摘要


腦血管疾病是臺灣地區國人十大死因中的第三位。缺血性中風(ischemic stroke)是腦血管疾病最主要的類型,約佔70%。缺血性中風的發生與動脈粥狀硬化有極大的關聯,動脈粥狀硬化不僅可能造成血管內徑的狹窄,影響血液流動,其血管內膜的粥狀硬化斑塊亦可能脫落形成血栓而阻塞腦部血流。血小板衍生生長因子C (Platelet-derived growth factor C, PDGFC)參與包括單核球轉移、巨噬細胞分化、平滑肌細胞轉移與增生以及泡沫細胞形成等動脈粥狀硬化形成的過程,扮演影響動脈粥狀硬化的重要角色。因此,本研究目的為探討PDGFC與傳統危險因子對缺血性中風的獨立與交互作用。   研究對象包括1215位缺血性中風病患與1215位經年齡及性別配對的對照族群。資料收集包括以標準化的流程使用結構式問卷收集基本人口學、相關危險因子、疾病史與用藥史等資料,以及利用禁食八小時靜脈血測量相關血液生化值資料。基因多形性的判定是使用聚合?○s鎖反應(polymerase chain reaction, PCR)與限制片段長度多形性方法(restriction fragment length polymorphism, RFLP)。使用T檢定及卡方檢定比較兩組資料的差異,並使用邏輯斯迴歸模式分析PDGFC基因多形性和傳統危險因子與缺血性中風的關係。   研究結果顯示缺血性中風的危險因子包括抽菸、喝酒、高血壓、糖尿病、血脂異常、心臟疾病及腹部肥胖。基因多形性分析部分,PDGFC三個基因多形性與罹患缺血性中風的風險均有顯著的相關。首先rs3815861基因多形性攜帶CC基因型者,相較於TT及TC基因型者有1.51倍罹患缺血性中風的風險;rs1425486基因多形性攜帶TT基因型者,相較於CC及CT基因型者有0.74倍罹患缺血性中風的風險;rs3733486基因多形性攜帶CT及TT基因型者,相較於CC基因型者有0.69倍罹患缺血性中風的風險,均達統計顯著水準。此外,PDGFC rs1425486及rs3733486危險基因數與高血壓和糖尿病對罹患缺血性中風的風險存在著交互作用。不論在有無高血壓或糖尿病的分層下,隨著攜帶PDGFC rs1425486及rs3733486危險基因數的增加,其罹患缺血性中風的危險性也隨之增加,且存在著顯著的趨勢效應。   總結以上,本研究顯示PDGFC三個基因多形性與缺血性中風的發病風險存在顯著的相關;而其風險與高血壓、糖尿病存在累乘協同效應。

並列摘要


Cerebrovascular disease is the third leading death cause in Taiwan. Ischemic stroke is the major subtype of cerebrovascular disease (about 70%). Atherosclerosis including inflammation, cell adhesion, platelet function, thrombosis, and endothelial dysfunction is a well-known risk factor of ischemic stroke. Recent studies have shown that PDGFC is expressed in monocytes, macrophages, VSMCs, foam cell, and human atherosclerotic lesions, and has been involved in almost every stage of atherosclerosis development and progression. Therefore, we investigate the relationship between genetic polymorphisms of PDGFC including rs3815861, rs1425486, and rs3733486 and risk of ischemic stroke. The case-control study was conducted with 1215 ischemic stroke patients and 1215 healthy controls frequency matched by case’s age and sex. All subjects were interviewed by well-trained research assistants to collect questionnaire data including demographic characteristics, conventional vascular risk factors and disease history. Serum biochemistry tests including fasting glucose and lipid profiles. We genotyped three genetic polymorphisms of PDGFC using polymerase chain reaction-restriction fragments length polymorphism (PCR-RFLP) method. Data were compared using Student’s t-test and chi-square test. Logistic regression was used to estimate the odds ratio (OR) and 95% confidence interval (95% CI) of risk factors related with ischemic stroke. Study results showed that risk factors of ischemic stroke includes smoking, alcohol drinking, hypertension, diabetes mellitus, dyslipidemia, heart disease and central obesity. Study subjects with the CC genotype of rs3815861 significantly increased the risk of ischemic stroke(OR=1.51, 95%CI: 1.10-2.08). In addition, study subjects carried with the TT genotype of rs1425486 and with the T allele of rs3733486 significantly decreased the risk of ischemic stroke, showing OR=0.74, 95%CI: 0.55-0.99 and OR=0.69, 95%CI: 0.55-0.86, respectively. Moreover, we found a significant joint effect between number of risk genotypes of PDGFC rs1425486 and rs3733486, hypertension and diabetes mellitus on the risk of ischemic stroke. In conclusion, our results showed significant association between PDGFC three genetic polymorphisms and the risk of ischemic stroke. We also found a significant joint effect between rs1425486 and rs3733486 of PDGFC, hypertension and diabetes mellitus on the risk of ischemic stroke.

參考文獻


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