發(fā)布時間：2018-05-30 06:28

  本文選題：偏頭痛 + 環(huán)氧化酶��； 參考：《南京醫(yī)科大學》2017年博士論文

【摘要】：背景:偏頭痛是臨床常見的原發(fā)性頭痛,其特點為反復發(fā)作性,多為中重度頭痛,一般持續(xù)4-72小時,常伴有惡心、嘔吐、畏光、畏聲。在中國大陸地區(qū)發(fā)病率達9.3%。環(huán)氧化酶(cyclooxygenase,COX)又稱前列腺素合成酶,是花生四烯酸在各種刺激作用下轉(zhuǎn)變?yōu)榍傲邢偎氐年P(guān)鍵酶。COX-2在炎癥因子誘導下表達,促進前列腺素合成參與炎性疼痛。臨床研究結(jié)果提示偏頭痛組COX-2的表達量顯著高于對照組,且選擇性COX-2抑制劑與非選擇性COX抑制劑治療偏頭痛急性發(fā)作無顯著差異。所以說,COX-2在偏頭痛病理生理過程中起著重要的作用。人類COX-2基因位于染色體1q25.2-q25.3上,由位于第10個外顯子長度約8.3 KB的片段構(gòu)成。COX-2基因的功能性單核苷酸多態(tài)性(single-nucleotide polymorphisms,SNPs)被廣泛研究,其中包括啟動子區(qū)的-765 GC(rs20417),編碼區(qū)的-1759 GA(Gly587Arg,rs3218625)以及 3'UTR區(qū)的-8473 CT(rs5275)。這3個SNPs與COX-2的表達水平和轉(zhuǎn)錄活性相關(guān)。有研究報道COX-2單核苷酸多態(tài)性與多種COX-2參與發(fā)病機制的疾病相關(guān),包括支氣管哮喘、冠狀動脈疾病、腦梗死,卒中亞型等等。但是目前涉及-765 GC/-1759 GA/-8473 CT突變和偏頭痛發(fā)病風險,特別是在中國漢族人群中的研究,卻鮮有報道。目的:研究中國漢族人群中COX-2-765 GC/-1759 GA/-8473 CT基因多態(tài)性和偏頭痛發(fā)病風險的關(guān)系。方法:本課題設(shè)計了一項基于醫(yī)院的病例對照研究,共包含110例偏頭痛患者,以及108例年齡和性別相匹配的非偏頭痛對照,采用連接酶檢測反應(yīng)(LDR-PCR)測序分型技術(shù)的方法來鑒別COX-2-765 GC、-1759 GA和-8473 CT單核苷酸多態(tài)性的基因型。結(jié)果:對照組人群中三種多態(tài)性的基因型和等位基因頻率分布符合Hardy-Weinberg 平衡(P值分別為 0.884,0.215,0.689)。COX-2-1759GA 的基因型和等位基因的分布在病例組和對照組之間存在顯著差異(P值分別為0.038和0.040)。相比于攜帶A/G基因型的個體,攜帶基因型G/G的個體顯著地增加了偏頭痛的發(fā)病風險(OR =8.720,95%CI= 1.072-70.960,P = 0.038);對照組攜帶COX-2 1759A等位基因的頻率顯著高于病例組,所以與1759G等位基因相比,COX-2 1759A等位基因降低了偏頭痛的發(fā)病風險(OR=0.119,95%CI=0.015-0.957,P=0.040)。然而我們沒有發(fā)現(xiàn)-765GC 和-8473TC 多態(tài)性與偏頭痛發(fā)病風險之間的關(guān)系。結(jié)論:本研究結(jié)果提示在中國漢族人群中COX-2 1759A等位基因可能是偏頭痛的一個獨立的保護因素。
[Abstract]:Background: migraine is a common clinical primary headache, characterized by recurrent attacks, mostly moderate and severe headache, usually lasting 4-72 hours, often accompanied by nausea, vomiting, photophobia, fear of sound. The incidence rate in mainland China is 9.3%. Cyclooxygenase, also known as prostaglandin synthase, is the key enzyme of arachidonic acid to change to prostaglandin under various stimuli. COX-2 is induced by inflammatory factors and promotes prostaglandin synthesis to participate in inflammatory pain. The clinical results showed that the expression of COX-2 in migraine group was significantly higher than that in control group, and there was no significant difference between selective COX-2 inhibitor and non-selective COX inhibitor in the treatment of migraine acute attack. Therefore, COX-2 plays an important role in the pathophysiological process of migraine. Human COX-2 gene is located on chromosome 1q25.2-q25.3. The functional single nucleotide polymorphisms of COX-2 gene, composed of a fragment of about 8.3KB in exon 10, have been extensively studied. These include -765 GCU rs20417 in the promoter region, -1759 GAGly587Arg rs3218625 in the coding region, and -8473 CTS5275 in the 3'UTR region. These three SNPs were related to the expression level and transcription activity of COX-2. COX-2 single nucleotide polymorphisms have been reported to be associated with a variety of diseases involved in the pathogenesis of COX-2, including bronchial asthma, coronary artery disease, cerebral infarction, stroke subtype and so on. However, there are few reports of-765 GC/-1759 GA/-8473 CT mutation and migraine risk, especially in Chinese Han population. Objective: to study the association between COX-2-765 GC/-1759 GA/-8473 CT gene polymorphism and migraine risk in Chinese Han population. Methods: a hospital-based case-control study was designed, including 110 migraine patients and 108 age-matched non-migraine controls. The genotypes of single nucleotide polymorphisms (SNP) of COX-2-765 GCn-1759GA and -8473CT were identified by ligase detection of LDR-PCR sequencing technique. Results: the genotypic and allele frequencies of the three polymorphisms in the control group were in accordance with the Hardy-Weinberg equilibrium P value of 0.884A 0.2150.689% .COX-2-1759GA. There were significant differences in genotype and allele distribution between the case group and the control group (P = 0.038 and P = 0.040, respectively). Compared with the individuals carrying the A / G genotype, the individuals with the genotype G / G significantly increased the risk of migraine. The frequency of allele COX-2 1759A in the control group was significantly higher than that in the case group, and the risk of migraine was significantly higher than that in the control group (OR = 8.720 / 95 CI = 1.072-70.960A P = 0.038). So compared with 1759G allele, COX-2 1759A allele reduced the risk of migraine. However, we did not find any association between the-765GC and-8473TC polymorphisms and the risk of migraine. Conclusion: the results suggest that COX-2 1759A allele may be an independent protective factor for migraine in Chinese Han population.
【學位授予單位】：南京醫(yī)科大學
【學位級別】：博士
【學位授予年份】：2017
【分類號】：R747.2

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本文編號：1954279