LTA4H基因多態(tài)性對(duì)動(dòng)脈粥樣硬化型腦梗死的影響
本文選題:缺血性腦卒中 + 白三烯A4水解酶 ; 參考:《青島大學(xué)》2014年碩士論文
【摘要】:腦卒中是一種嚴(yán)重威脅人類(lèi)生命健康的常見(jiàn)的神經(jīng)系統(tǒng)疾病,缺血性腦卒中的發(fā)病除與傳統(tǒng)的危險(xiǎn)因素如高血糖、高血壓、高血脂、吸煙等相關(guān)以外,遺傳變異也是其重要的發(fā)病原因,環(huán)境與遺傳因素可單獨(dú)對(duì)缺血性腦卒中作用外,也可通過(guò)兩者的相互作用增加易感性。作為白三烯生成過(guò)程中一個(gè)重要限速酶的白三烯A4水解酶(LTA4),許多對(duì)其基因多態(tài)性的研究多集中在癌癥及呼吸系統(tǒng)疾病,很少有研究探討其與缺血性腦卒中的關(guān)系,本研究旨在以LTA4H作為候選基因,探討其基因多態(tài)性對(duì)動(dòng)脈粥樣硬化型缺血性腦卒中的影響,為該病的個(gè)體預(yù)防及治療提供臨床資料。 研究目的:探討白三烯A4水解酶基因多態(tài)性對(duì)動(dòng)脈粥樣硬化型梗死發(fā)病率的影響。 研究方法:本實(shí)驗(yàn)采用病例對(duì)照研究和分子流行病學(xué)研究方法,選擇山東地區(qū)人群為研究對(duì)象,病例組為2010年9月到2012年10期間于月青島大學(xué)醫(yī)學(xué)院附屬醫(yī)院住院的動(dòng)脈粥樣硬化型腦梗死患者450例,本實(shí)驗(yàn)納入病例經(jīng)臨床、MRA及頸部血管超聲或頭頸部CTA或全腦血管造影DSA檢查均符合全國(guó)第四屆腦血管病會(huì)議修訂的腦血管病診斷標(biāo)準(zhǔn)及1993年由美國(guó)Adams等制訂的TOAST(the trial of or910172in acute stroke treatment)分型標(biāo)準(zhǔn)。對(duì)照組來(lái)自同期本科室及其他科室、健康體檢中心的性格、年齡相匹配的非缺血性腦卒中者400例,應(yīng)用聚合酶鏈反應(yīng)一限制性片段長(zhǎng)度多態(tài)性(PCR-RFLP)方法,檢測(cè)LTA4H基因rs6538697位點(diǎn)的基因多態(tài)性并行結(jié)果分析。 研究結(jié)果:病例組和對(duì)照組LTA4Hrs6538697T/C位點(diǎn)基因型分布差異具有統(tǒng)計(jì)學(xué)意義(X2=4.49,P0.05)。病例組C等位基因頻率顯著高于對(duì)照組,T等位基因頻率明顯低于對(duì)照組,差異有統(tǒng)計(jì)學(xué)意義(X2=7.27,P0.05),,經(jīng)logistic回歸方法排除腦卒中的傳統(tǒng)危險(xiǎn)因素如高血壓、糖尿病、甘油三酯(TG)、總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)影響后,LTA4Hrs6538697C等位基因攜帶者動(dòng)脈粥樣硬化型腦梗死易感性增高1.34倍(OR=1.34,95%CI1.010-1.786, P0.05)。 結(jié)論:LTA4Hrs6538697C/T基因多態(tài)性與山東地區(qū)人群動(dòng)脈粥樣硬化型腦梗死具有相關(guān)性,rs6538697T-C等位基因突變能增加動(dòng)脈粥樣硬化型腦梗死的發(fā)病風(fēng)險(xiǎn)。
[Abstract]:Stroke is a common nervous system disease that seriously threatens human life and health. The incidence of ischemic stroke is related to traditional risk factors such as hyperglycemia, hypertension, hyperlipidemia, smoking and so on. Genetic variation is also an important cause of ischemic stroke. Environmental and genetic factors can not only play a role in ischemic stroke, but also increase susceptibility through the interaction of the two factors. As an important rate-limiting enzyme in the formation of leukotriene, leukotriene A4 hydrolase LTA4 has been studied mostly in cancer and respiratory diseases. The purpose of this study was to investigate the effect of LTA4H gene polymorphism on atherosclerotic ischemic stroke, and to provide clinical data for individual prevention and treatment of Atherosclerotic stroke. Objective: to investigate the effect of leukotriene A 4 hydrolase gene polymorphism on the incidence of atherosclerotic infarction. Methods: a case-control study and a molecular epidemiology study were conducted to study the population in Shandong province. The case group consisted of 450 patients with atherosclerotic cerebral infarction hospitalized in the affiliated Hospital of Medical College of Qingdao University from September 2010 to October 2012. The clinical MRA, cervical vascular ultrasound, head and neck CTA or DSA examination were in accordance with the revised diagnostic criteria of cerebrovascular disease and TOAST(the developed by Adams et al in 1993. Trial of or910172in acute stroke treatment) typing standard. In the control group, 400 patients with non-ischemic stroke were collected from our department and other departments and health examination centers in the same period. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used. The gene polymorphism of rs6538697 locus of LTA4H gene was analyzed by parallel analysis. Results: the difference of genotype distribution of LTA4Hrs6538697T/C locus between case group and control group was statistically significant. The frequency of C allele in the case group was significantly higher than that in the control group, and the frequency of T allele was significantly lower than that in the control group. The difference was statistically significant. The traditional risk factors of stroke such as hypertension and diabetes were excluded by logistic regression. The susceptibility to atherosclerotic cerebral infarction was 1.34 times higher in patients with TGG, TC, LDL-C, LTA4Hrs6538697C alleles, and 1.34-95 CI 1.010-1.786, P 0.055.The results showed that there was no significant difference between LTA4Hrs6538697C allele carriers and patients with atherosclerotic cerebral infarction (LTA4Hrs6538697C). Conclusion the allele mutation of rs6538697T-C allele may increase the risk of atherosclerotic cerebral infarction in Shandong area.
【學(xué)位授予單位】:青島大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2014
【分類(lèi)號(hào)】:R743.3
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