本文選題：帕金森病　切入點(diǎn)：基因突變　出處：《大連醫(yī)科大學(xué)》2014年碩士論文　論文類型：學(xué)位論文

【摘要】：目的：本研究選擇攜帶LRRK2G2385R或R1628P基因突變類型的散發(fā)性PD患者，與未攜帶上述兩種突變類型的散發(fā)性PD患者進(jìn)行比較，旨在了解LRRK2兩種基因突變類型在中國散發(fā)性PD人群中的發(fā)生率，基因突變攜帶者的性別、發(fā)病年齡、臨床癥狀與非攜帶者是否有不同，以及基因突變對散發(fā)性PD人群在藥物療效方面的影響。 方法：選取2009年9月~2012年5月大連醫(yī)科大學(xué)附屬第一醫(yī)院門診及住院病人中診斷為原發(fā)性帕金森病并進(jìn)行帕金森病相關(guān)基因檢測的患者135例，均符合1992年英國帕金森病協(xié)會（UK-PDS）腦庫標(biāo)準(zhǔn)，且無帕金森病家族史，，并由患者本人或其法定監(jiān)護(hù)人簽署基因檢測知情同意書，從中選取臨床隨訪兩年以上且有詳細(xì)臨床資料者86例。根據(jù)基因檢測結(jié)果將86例患者分為兩組，存在LRRK2G2385R或LRRK2R1628P基因突變?yōu)長RRK2-PD組，不存在LRRK2G2385R、LRRK2R1628P基因突變者為IPD組。取患者肘靜脈血約15ml，其中抗凝血（枸櫞酸鈉抗凝）8~10ml，不抗凝血4~5ml，分裝入2個一次性使用人體靜脈血采集容器中，管體標(biāo)簽均標(biāo)明患者姓名、年齡及抽血時間，采用常規(guī)酚-氯仿法抽提DNA，放置于-20℃保存，應(yīng)用PCR結(jié)合DNA測序的方法對LRRK2基因突變進(jìn)行分析。收集上述86例患者的臨床資料，包括：性別、發(fā)病年齡、病程、運(yùn)動癥狀（靜止性震顫、肌強(qiáng)直、運(yùn)動遲緩、姿勢步態(tài)異常等）、非運(yùn)動癥狀（便秘、睡眠行為障礙、焦慮、抑郁、認(rèn)知功能障礙等）、運(yùn)動并發(fā)癥（異動癥、劑末現(xiàn)象、肌張力障礙、晨僵、癥狀波動等）及在隨訪兩年內(nèi)應(yīng)用的抗帕金森藥物名稱，其中抑郁癥狀使用流調(diào)中心抑郁量表（Center for Epidemiologic Studies Depression Scale, CES-D）評估，＞16分表示有抑郁癥狀，認(rèn)知功能障礙使用簡易智能精神狀態(tài)檢查量表（Mini-Mental State Examination, MMSE）評估，＜24分表示有認(rèn)知功能障礙，隨訪前后病情使用統(tǒng)一帕金森評定量表（Unified Parkinson’s Disease RatingScale, UPDRS3.0）評估，包括UPDRS總分、UPDRSⅠ、Ⅱ、Ⅲ、Ⅳ部分評分，其中UPDRSⅡ、Ⅲ部分評分在“開期”進(jìn)行評定。計算LRRK2基因突變的陽性率，比較LRRK2-PD組與IPD組在發(fā)病年齡、病程、運(yùn)動癥狀、非運(yùn)動癥狀、運(yùn)動并發(fā)癥、左旋多巴的療效及隨訪前后UPDRS各部分評分等方面是否存在差異。所有數(shù)據(jù)采用SPSS13.0統(tǒng)計軟件進(jìn)行統(tǒng)計學(xué)分析。 結(jié)果： LRRK2G2485R基因突變陽性率8.89%（12例），LRRK2R1628P基因突變陽性率1.48%（2例）。 LRRK2-PD組與IPD組患者的性別、發(fā)病年齡、病程及隨訪前Hoehn-Yahr分期、UPDRS各項(xiàng)評分均無統(tǒng)計學(xué)差異（P＞0.05）。運(yùn)動癥狀：兩組患者在靜止性震顫（LRRK2-PD組78.6%，IPD組87.5%）、肌強(qiáng)直（LRRK2-PD組92.9%，IPD組88.9%）、運(yùn)動遲緩（LRRK2-PD組100%，IPD組93.1%）及姿勢步態(tài)異常（LRRK2-PD組78.6%，IPD組80.6%）等運(yùn)動癥狀的發(fā)生率方面差異無統(tǒng)計學(xué)意義（P＞0.05）。非運(yùn)動癥狀：兩組患者在便秘（LRRK2-PD組57.1%，IPD組77.8%）、睡眠行為障礙（LRRK2-PD組71.4%，IPD組88.9%）、焦慮（LRRK2-PD組35.7%，IPD組38.9%）、抑郁（LRRK2-PD組42.9%，IPD組50.0%）及認(rèn)知功能障礙（LRRK2-PD組0.0%，IPD組8.3%）等非運(yùn)動癥狀的發(fā)生率方面差異無統(tǒng)計學(xué)意義（P＞0.05），兩組患者的CES-D評分（LRRK2-PD組17.29±11.12分，IPD組16.19±9.67分）及MMSE評分（LRRK2-PD組26.86±2.18分，IPD組27.24±2.69分）差異無統(tǒng)計學(xué)意義（P＞0.05）。運(yùn)動并發(fā)癥：兩組患者在異動癥（LRRK2-PD組14.3%，IPD組6.9%）、劑末現(xiàn)象（LRRK2-PD組14.3%，IPD組5.6%）、肌張力障礙（LRRK2-PD組14.3%，IPD組9.7%）、晨僵（LRRK2-PD組7.1%，IPD組15.3%）及癥狀波動（LRRK2-PD組14.3%，IPD組6.9%）等運(yùn)動并發(fā)癥的發(fā)生率方面差異無統(tǒng)計學(xué)意義（P＞0.05）。對左旋多巴治療的反應(yīng)：兩組患者對左旋多巴的有效率（LRRK2-PD組91.7%，IPD組87.5%）差異無統(tǒng)計學(xué)意義（P＞0.05）。隨訪前后UPDRS各部分評分：LRRK2-PD組隨訪前后UPDRS總（隨訪前31.36±16.78分，隨訪后29.50±15.83分）、Ⅰ部分（隨訪前2.21±1.76分，隨訪后1.79±1.12分）、Ⅱ部分（隨訪前8.57±6.16分，隨訪后6.29±4.12分）、Ⅲ部分（隨訪前19.07±9.68分，隨訪后20.64±10.82分）、Ⅳ部分（隨訪前1.21±1.37分，隨訪后0.50±0.94分）評分差異無統(tǒng)計學(xué)意義（P＞0.05）。IPD組隨訪前后UPDRS總（隨訪前36.06±17.77分，隨訪后35.75±11.20分）、Ⅰ部分（隨訪前2.49±1.96分，隨訪后2.19±1.15分）評分差異無統(tǒng)計學(xué)意義（P＞0.05），Ⅱ部分（隨訪前10.71±5.71分，隨訪后8.43±4.07分）、Ⅳ部分（隨訪前1.36±1.83分，隨訪后0.92±1.34分）評分差異有統(tǒng)計學(xué)意義（P＜0.05），Ⅲ部分（隨訪前21.64±11.56分，隨訪后24.39±7.93分）評分差異有統(tǒng)計學(xué)意義（P＜0.05）。 結(jié)論： 1.散發(fā)性帕金森病人群LRRK2G2385R、LRRK2R1628P基因突變的陽性率分別為8.89%、1.48%。 2.散發(fā)性帕金森病人群LRRK2基因突變攜帶者與非攜帶者的臨床特征無明顯差異。 3.散發(fā)性帕金森病人群LRRK2基因突變攜帶者與非攜帶者的藥物療效不同。
[Abstract]:Objective: This study carry LRRK2G2385R or R1628P gene mutation in sporadic PD patients, compared with the above two types of mutations did not carry sporadic PD patients, in order to understand the LRRK2 two gene mutation in sporadic PD China population, gene mutation carriers of gender, age of onset, clinical symptoms with non carriers are different, and the effect of gene mutation on PD in patients with sporadic drug efficacy.
Methods: the patients of First Affiliated Hospital of Dalian Medical University in May and September 2009 ~2012 inpatients diagnosed as idiopathic Parkinson's disease and Parkinson's disease related genes were detected in 135 patients, are in line with the 1992 British Parkinson Disease Association (UK-PDS) gasoft standard, and no family history of Parkinson's disease, and the patients themselves or their legal guardians signed gene detection of informed consent, selected from more than two years clinical follow-up and detailed clinical data of 86 cases. According to the gene detection results of 86 patients were divided into two groups, the presence of LRRK2G2385R or LRRK2R1628P gene mutation for LRRK2-PD group, no LRRK2G2385R, LRRK2R1628P gene mutation for IPD group. Patients in venous blood of about 15ml among them, the anticoagulant (sodium citrate) 8~10ml, without anticoagulant 4~5ml, divided into 2 disposable human venous blood collection container, the tube body tags are marked The patient's name, age and blood time, using conventional phenol chloroform extraction DNA, placed in -20 C preservation, application of PCR method combined with DNA sequencing of LRRK2 gene mutations were analyzed. The clinical data, collected the 86 patients including gender, age, disease duration, motor symptoms (resting tremor, myotonia. The slow movement, posture and gait abnormalities), non motor symptoms (constipation, sleep behavior disorder, anxiety, depression, cognitive dysfunction), motor complications (dyskinesia, the phenomenon of the agent, dystonia, symptoms of morning stiffness, wave etc.) and its application in the follow-up within two years of the anti Parkinson drug name, use the symptom of depression the center for Epidemiological Studies Depression Scale (Center for Epidemiologic Studies Depression Scale, CES-D) assessment, > 16 points represented with depressive symptoms, cognitive impairment using mini mental state examination (Mini-Mental State Examina Tion, MMSE < 24) evaluation, said the cognitive dysfunction, follow-up before and after using the unified Parkinson Disease Rating Scale (Unified Parkinson s Disease RatingScale, UPDRS3.0) assessment, including the total score of UPDRS, UPDRS I, II, III, IV Part II score, the UPDRS score were assessed in part III, "on". Calculated the positive rate of LRRK2 gene mutation, LRRK2-PD group and IPD group in age, duration of disease, motor symptoms, non motor symptoms and motor complications before and after treatment and follow-up of levodopa and other aspects of each part of the UPDRS score difference. All data were statistically analyzed by SPSS13.0 statistical software.
Result錛

本文編號：1599653