【作者】 赵燕燕；

【导师】 刘卫国；

【作者基本信息】 南京医科大学 ， 神经病学， 2011， 硕士

【摘要】 目的:探讨PARK16基因多态性(SNP)与帕金森病(PD)易患性的关系,分析其SNP的基因型和等位基因频率及不同基因型的优势比(Odds Ratios)和其临床特征。方法:采用病例-对照研究选择PD患者407例和516名健康对照,利用TaqMan荧光定量PCR方法检测中国汉族人群中PARK16基因Rs947211和Rs823128基因多态性,并对不同基因型临床资料进行分析。结果:1 PARK16基因的多态性位点Rs947211在PD组基因型频率为:GG 35.4%(144/407)、AG 45.7%(186/407)、AA 18.9%(77/226),对照组分别为26.4%(136/516)、53.3%(275/516)、20.3%(105/516),2组基因型频率差异具有统计学意义(基因型X~2=8.97,P=0.011;等位基因X~2=5.03,P=0.027)。采用Logistic回归校正性别、年龄后,以野生型GG为参照,其PD组AG OR值=0.63,95% CI:0.47-0.85,P=0.002;AA OR=0.68,95% CI:0.47-0.99,P=0.046。暴露于A等位基因型(AA+AG)的OR=0.64(95% CI: 0.48-0.85,P=0.002)。将PD组进一步按照家族史分层分析发现,散发性PD PARK16 rs947211基因型与对照组有统计学差异(OR(MH)=0.66, 95%CI: 0.50-0.86,X~2=8.85,P=0.003)。2 Rs823128在PD组基因型频率分布为AA 71.6% (280/391),AG 25.1%(98/391),GG 3.3% (13/391),等位基因频率:A 84.1%,G 15.9%,对照组为:AA 75.2% (312/415),AG 22.2% (92/415),GG 2.7% (11/415),等位基因频率:A 86.3%,G 13.7%,两组基因型和等位基因频率均无统计学意义(基因型X~2=1.37,P=0.503;等位基因X~2=1.44,P=0.233)。3 PD组PARK16 rs947211和rs8231283三种基因型在性别、年龄、发病年龄、病程、有无家族史、主要特征、帕金森病统一评分量表Ⅲ(UPDRSⅢ)、哈密顿抑郁量表(HAMD)、哈密顿焦虑量表(HAMA)、抑郁自评量表(SDS)、焦虑自评量表(SAS)、帕金森病睡眠量表(PDSS)、帕金森病非运动症状量表(PDNMS)、蒙特利尔认知量表(MOCA)、简易精神状态检查量表(MMSE)临床方面均无统计学意义(P>0.05)。结论:中国汉族人群中PARK16基因与PD易患性相关。目的:探讨初诊帕金森病(PD)患者非运动症状量表(NMSQuest)细项和NMS症状群(NMSQ-D)的发生和分布情况及与PD的临床基本资料和各个量表的关系。方法:收集首次就诊的PD患者61例,在未服用抗PD药物的前提下进行PD基本信息登记和相关量表评估,并与89名正常对照组的NMS相比较。结果: PD组96.72%的患者存在NMS,PD组NMS平均发生数(9.1±5.2)、PD轻度组(7.2±3.7)和PD中度组(12.2±4.6)与正常对照组(2.9±2.5)相比有显著差异(P<0.01)。PD组中以近记忆力下降(62.3%,38例)、注意力下降(57.4%,35例)、便秘(49.2%,30例)为最常见,与健康对照组均有显著差异(P<0.01)。PD轻度组以近记忆力下降(64.3%,27例)、注意力下降(52.4%,22例)、便秘(42.9%,18例)和入睡难或易醒(42.9%,18例)为最常见,除入睡难或易醒,其余均与对照组有显著差异(P<0.01)。PD中度组以注意力下降(64.7%,11例)、近记忆力下降(58.8%,10例)、便秘(58.8%,10例)和夜梦增多(58.8%,10例)为最常见,除近记忆力下降外,其余均与健康对照组均有显著差异(P<0.01)。NMS症状群(NMSQ-D)经Kruskal-Wallis检验发现与之关系最密切的是H-Y分期,其次是病程、UPDRS-Ⅲ,与年龄、发病年龄无差异。NMSQuest与H-Y分期(r=0.339,P<0.01)、SDS(r=0.724,P<0.01)、SAS(r=0.700,P<0.01)成正相关;与PDSS (r=-0.578,P<0.01)负相关;与年龄、发病年龄、性别、病程、UPDRS-Ⅲ评分、MOCA无关。结论: PD初诊患者非运动症状复杂多样,发生率明显高于正常人,故需重视初诊患者的非运动症状,在早期就加以干预和治疗。更多还原

【Abstract】 Objective: To investigate the association between PARK16 gene polymorphism and Parkinson’s disease (PD) susceptibility in Chinese Han population, and to analyze its SNP genotypes, frequencies and odds ratios(OR) of different genotypes.Methods: The association between two SNP loci in PARK16 gene (Rs947211, Rs823128) and PD susceptibility was investigated by TaqMan quantitative polymerase chain reaction (PCR) in 407 PD patients and 516 healthy controls. Clinical data was also analyzed. Results:1 In PD group, three genotypes of Rs947211 (GG, AG and AA) accounted for 35.4%, 45.7%, 18.9%, Control group 26.4%, 53.3%, 20.3% respectively, two groups were significant differences (P<0.05). GG genotype as the reference, after adjusting age and gender, OR value of AG of PD group was 0.63 (95% CI: 0.47-0.85, P=0.002) and OR of AA genotype was 0.68 (95% CI: 0.47-0.99, P=0.046). Exposure to the A allele (AA+AG), and its OR was 0.64 (95% CI: 0.48-0.85, P=0.002). Subsequently, it could be concluded that there was a lower risk factor in sporadic PD than familiar PD (OR (MH) =0.66, 95% CI: 0.50-0.86, X~2=8.85, P=0.003).2 The frequencies of genotypes and Allele of Rs823128 in PD group were no significantly different with control group(X~2=1.37, P=0.503; X~2=1.44, P=0.233).3 Clinical features of the Rs947211 and Rs823128 in three genotypes were further analyzed, and there were no differences between the clinical characteristics in the patients in the three genotypes for genders, ages, age-at-onset, disease durations, family histories, cardinal features (resting tremor, rigidity and mixed symptoms), scores of Hoehn-Yahr stage, UPDRSⅢscores (on-stage), HAMD scores, HAMA scores, SDS scores, SAS scores, PDSS scores, PDNMS scores, MOCA scores and MMSE scores. Conclusion: PARK16 is associated with PD patients in Chinese Han population. Objective: To investigate the incidence, distribution of non-motor symptoms (NMS) and NMSQuest-Details (NMSQ-D) in patients with newly diagnosed PD, and its relationship with clinical features and various scales.Methods: 61 PD patients without taking any drugs and 89 normal controls were collected in outpatient visits, and their clinic information and related scales were also evaluated.Results: 96.7% PD total patients presented with NMS, decreased recent memory (62.3%, n=38), decreased attention (57.4%, n =35), and constipation (49.2%, n=30) were the most common in PD group, there were significantly different between PD group and Normal group (P <0.01), so did the moderate and mild groups of PD. NMSQuest average score of the PD group (9.1±5.2), PD moderate disease group of NMS (12.2±4.6) and mild group (7.2±3.7) were significantly higher than the control group (2.9±2.5) (P <0.01). We also found that NMSQust Details (NMSQ-D) were most closely with the HY stage by Kruskal Wallis test, the followed were the course of disease and UPDRS-Ⅲ, no difference was found between age and age of onset. NMSQuest and HY stage (r = 0.339, P <0.01), SDS (r = 0.724, P <0.01), SAS (r = 0.700, P <0.01) were Positive correlation; And PDSS (r =- 0.578, P <0.01) was negative correlation; age, age at onset, gender, duration, UPDRS-Ⅲscore and MOCA had nothing to do with NMSQuest.Conclusion: Non-motor symptoms in patients with newly diagnosed PD were complex and diverse, which were significantly higher than normal, and people are susceptible to ignore them, so we need to pay attention to them and treating at the early-stage PD diseases.更多还原