人類端粒酶反轉錄酶及端粒酶RNA模板基因多形性與早發型缺血性中風之相關性研究

Association study on genetic polymorphisms of human telomerase reverse transcriptase, telomerase RNA component, and early-onset ischemic stroke

林宛瑩(Wan-Ying Lin)

指導教授 ： 謝芳宜

臺北醫學大學/公共衛生暨營養學院/公共衛生學研究所/碩士(2012年)

https://doi.org/10.6831/TMU.2012.00162

摘要

早發型缺血性中風是造成年輕患者殘障及死亡的主要原因。動脈粥狀硬化為造成缺血性中風的成因之一，年齡為動脈粥狀硬化重要的危險因子，細胞老化則與動脈粥狀硬化具有相關性。端粒長度會隨著細胞週期而逐漸縮短，而端粒的長度和細胞衰老、動脈粥狀硬化具有相關性。端粒長度由人類端粒酶反轉錄酶(hTERT)及端粒酶RNA模板(TERC)來維持。因此本研究探討hTERT與TERC之基因多形性與罹患早發型缺血性中風的相關性。

研究結果顯示在校正年齡、性別、教育程度、高血壓病史、糖尿病病史、抽菸危險因子效應之後，攜帶TERC之rs12696304 C對偶基因者相對於攜帶GG基因型者有1.6倍(95%CI: 1.04-2.17)早發型缺血性中風的罹病風險，且有2.14倍(95%CI:1.01-2.29)小血管阻塞亞型之罹病風險。高血壓與TERC rs12696304之C對偶基因對於早發型缺血性中風也具有顯著加成協同作用。合併TERC rs12696304與hTERT rs2735940之可能危險基因組，發現在有高血壓病史、有或無心臟病病史、有抽菸者中，危險基因數和早發型缺血性中風之發生風險呈現顯著基因劑量效應關係。

總結，本研究發現攜帶TERC rs12696304之C對偶基因者有較高罹患早發型缺血性中風的風險，且該對偶基因與高血壓對於早發型缺血性中風有顯著的加成協同作用。攜帶該對偶基因者亦被觀察到有較高罹患小血管阻塞亞型之中風 風險。

關鍵字

早發型缺血性中風 ； 人類端粒酶反轉錄酶端粒酶RNA模板

並列摘要

Early-onset ischemic stroke is the main cause of disability and death in young adults. Atherosclerosis is one of the important factors involving in the development of ischemic stroke. Age is the well known risk factor of atherosclerosis. Furthermore, cell aging is related to atherosclerosis. It has been reported that telomeres are shortening with each cell cycle and related to cell aging and atherosclerosis. The telomere length is maintained by telomerase reverse transcriptase (hTERT) and telomerase RNA component (TERC). In this study, we aimed to investigate the relationship between the early-onset ischemic stroke and genetic polymorphism of hTERT and TERC.

This was a case-control study including 350 ischemic stroke patients age≦55 and 350 healthy controls frequency matched to cases with age and sex. All study subjects were interviewed by trained research assistants using a standard questionnaire including demographic data, conventional cardiovascular disease risk factors, and disease history. Biochemistry data were measured from fasting blood. Genotypes were determined by the method of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Multiple logistic regression models were used to analyse the relationship between the early-onset ischemic stroke and genetic polymorphism of hTERT and TERC

Our results showed that compared to TERC rs12696304 GG genotype, C allele carriers had a 1.6-fold risk of developing early-onset ischemic stroke and a 2.14-fold risk of developing ischemic stroke subtype small vessel occlusion after adjusted for age, gender, level of education, hypertensition, diabetes mellitus, heart disease, smoking, alcohol. An significant interaction has also been found between hypertension and TERC rs12696304 C allele. After combined the risk alleles of TERC rs12696304 and hTERT rs2735940, we found a significant gene dose response effect between the numbers of risk alleles and the risk of developing early-onset ischemic stroke.

In conclusion, our study found that TERC rs12696304 C allele carriers had a increased risk of developing early-onset ischemic stroke and this allele also had a significant joint effect with hypertension on the risk of developing early-onset ischemic stroke. TERC rs12696304 C allele carriers also had a increased risk of developing ischemic stroke subtype small vessel occlusion.

並列關鍵字

early-onset ischemic strokes ； human telomerase reverse transcriptas (hTERT) ； telomerase RNA component (TERC)

參考文獻

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