中国汉族早发型帕金森病人群PARK2基因突变的多态性分析

目的 观察散发性早发帕金森病(Parkinson s disease, PD)患者遗传易感基因突变的形式和分布,探讨易感基因突变在PD发病中的可能作用。 方法　病例组由30例散发性早发帕金森患者组成。抽取病人外周血提取DNA,以基因组DNA为模板, 通过PCR扩增PARK2基因的第1、4、6、7号外显子。比对PCR产物测序后的突变情况。结果 发现样本中存在突变,在正常人中存在单核苷酸多态性(single nucleotide polymorphism, SNP)。结论　PARK2基因外显子的突变是我国散发性早发PD患者的致病原因之一。     

PARK2基因变异致早发型帕金森病一例

患者男性,44岁,中专学历.因右侧肢体抖动、行动迟缓8年,加重10余天,于2020年6月20日人院.患者入院前8年无明显诱因出现右上肢不自主抖动、右下肢行动迟缓,右上肢摆臂动作减少,洗脸、系纽扣、穿衣等精细活动缓慢,其余活动正常,无日间症状波动,无肢体无力、感觉异常、构音障碍、饮水呛咳等.外院门诊诊断为帕金森综合征,予...     

PAL2G6基因点突变的早发型帕金森病1例报道并文献复习

目的 报道1例磷脂酶A2第6型基因(Phospholipase A2 type 6,PLA2G6)基因点突变导致的早发型帕金森病,并分析该基因突变患者的临床异质性。方法 应用全外显子测序结合一代测序验证方法对1个家系的6名成员进行基因检测,并结合文献总结PLA2G6基因点突变的早发型帕金森病的特点,以提高其早期诊断率。结果 在6名家系成员中先证者及其2子1女PAL2G6基因存在c.991G>T杂合突变和超氧化物歧化酶1(Superoxide dismutase 1,SOD1)基因存在c.208A>G杂合突变,结合患者的临床表现为运动迟缓和静止性震颤,¹¹C-CFT脑多巴胺转运体(Dopamine transporer,DAT)正电子发射断层显像(Positron emission tomography,PET)示双侧壳核、尾状核头多巴胺功能降低,诊断为早发型帕金森病。结论 早发型帕金森病需要及时进行基因检测,这样便于精准判断疾病,指导临床治疗。     

DJ-1基因多态性与帕金森病易感性的Meta分析

目的评价DJ-1基因多态性与帕金森病(PD)易感性的关系。方法检索知网、万方、Web of Science、Pub Med、EMBASE和Cochrane数据库,检索时间为2001年01月01日至2017年01月01日。确定文献纳入排除标准,并采用Newcastle-Ottawa Scale(NOS)进行质量评估,提取高质量文献的有用部分,使用stata12.0软件进行统计分析。结果共纳入12篇文献,收集到2895组病例和2817组对照,Meta分析结果显示,在帕金森病患者中,DJ-1基因g.168_185del缺失突变(OR=1.26,95%CI:1.06~1.50,P0.05)和c.G293A点突变(OR=2.74,95%CI:1.22~6.16,P0.05)均为PD的危险因素。在g.168_185del与PD相关性研究的亚组分析中,发现非中国人群g.168_185del多态性也是PD的危险因素(OR=1.41,95%CI:1.14~1.73,P0.05),但在中国人群中未发现其相关性(OR=0.98,95%CI:0.72~1.34,P0.05)。c.G293A与PD相关性病例对照研究中均为非中国人群,故未进行亚组分析。结论DJ-1基因g.168_185 del缺失突变和c.G293A点突变是PD的易感因素,但本Meta分析未发现DJ-1基因g.168_185 del缺失突变和c.G293A点突变与中国人群PD具有相关性。     

中国汉族人群PARK16基因多态性与帕金森病易患性的关联

目的 探讨PARK16基因单核苷酸多态性(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(OR)和其临床特征.方法 采用病例-对照研究选择PD患者226例和362名健康对照,利用TaqMan荧光定量PCR方法检测中国汉族人群中PARKl6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 PARKl6基因的多态性位点Rs947211在PD组基因型频率为∶GG 34.1%(77/226)、AG 46.0%(104/226)、AA 19.9%(45/226),对照组分别为23.8%(86/362)、53.0%(192/362)、23.2%(84/362),2组基因型频率差异具有统计学意义(以野生型GG为参考,AG∶OR=0.57,95%CI 0.38～0.85,P=0.006;AA∶OR=0.55.95%CI,0.34～0.85,P=0.015).以PD组野生型GG为参照,暴露于A等位基因型(AA+AG)的OR=0.56,95%CI0.38～0.82,P=0.003.晚发型PD(LOPD)Rs947211的基因型频率与对照组比较差异亦有统计学意义(AG∶OR=0.46,95%C/0.27～0.78,P=0.004∶AA∶OR=0.35,95%C/0.18～0.68,P=0.002).PD组3种基因型在临床表现上差异没有统计学意义.Rs823128在PD组基因型频率分布与对照组差异无统计学意义(以野生型AA为参照,AG∶OR=1.12,95%CI0.75～1.68,P=0.568;GG∶OR=0.99,95%CI0.35～2.76,P=0.994).结论 中国汉族人群中PARK16基因与PD易患性相关.

Abstract：

Objective To investigate the association between PARK16 gene polymorphism and Parkinson's disease(PD)susceptibility in Chinese Han population.and to analyze its single-nucleotide polymorphism(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 226 PD patients and 362 healthy controls.Allele and genotype frequencies were calculated by the Chi-square test,and the clinical data were also analyzed.Results Three genotypes of Rs947211(GG,AG and AA)account for 34.1%(77/226),46.0%(104/226),19.9%(45/226)in the PD group,and 23.8%(86/362),53.0%(192/362),23.2%(84/362)in the control group,respectively.There was significant difference between two groups (P<0.05).Setting the GG genotype as the reference,OR values of AG and AA genotype were 0.57(95%CI0.38-0.85,P=0.006)and 0.55(95%CI 0.34-0.85,P=0.015),while the OR value for exposure to the A allele(AA+AG)was 0.56(95%CI0.38-0.82,P=0.003).Genotypes of Iate-onset PD were also significantly different from the controls(OR valne of AG=0.46,95%CI 0.27-0.78,P=0.004:OR value of AA=0.35.95%CI 0.18-0.68,P=0.002).And there was no diffefence in clinical features among the 3 genotypes. The frequency of Rs823128, another locus, in PD group was not significantly different from the control group( AA genotype as the reference, OR value of AG was 1. 12, 95% CI 0. 75-1.68, P = 0.568; OR value of GG was 0.99, 95% CI 0.35-2.76, P = 0.994). Conclusion Polymorphism of PARK 16 locus Rs947211 is associated with PD patients in Chinese Han population.     

120例帕金森病人痴呆的分析

本文回顾分析了120例帕金森病人病例资料,以此探讨帕金森病人痴呆的发病率及其相关的因素。     

NLRP3基因多态性与中国北方东部汉族人群帕金森病相关性研究

目的探讨Nod样受体家族蛋白3 (Nod-like receptor protein 3,NLRP3)rs4612666及rs7525979位点多态性与中国北方东部汉族人群帕金森病(Parkinson disease,PD)发病风险的相关性。方法采用病例对照研究,共招募400例PD患者(PD组)及400例健康对照者(对照组),应用聚合酶链反应-限制性片段长度多态性方法鉴定NLRP3基因SNPs位点rs4612666和rs7525979。结果 PD组rs4612666等位基因与对照组具有统计学差异,C等位基因频率低于对照组,降低发病风险(OR=0.794,95%CI:0.653～0.967,P=0.021),隐性遗传模型CC/TT+CT分布在PD组与对照组之间差异具有统计学意义(OR=0.667,95%CI:0.481～0.925,P=0.015)。亚组分析中,与对照组比较,女性PD组与早发型PD组等位基因分布差异具有统计学意义(P=0.003,P=0.018)。rs7525979位点的基因型分布和等位基因频率在PD组与对照组比较均无统计学差异(P>0.05)。结论在中国北方东部汉...     

帕金森病患者PINK1LRRK2基因单核苷酸多态性分析

目的 探讨PINK1基因rs45530340位点及LRRK2基因rs1491942位点单核苷酸多态性（single nucleotide polymorphism,SNP）与淮海地区汉族人群晚发散发性帕金森病（Parkinson＇s disease,PD）的相关性.方法 收集152例晚发散发性PD患者和160例年龄和性别相匹配的健康对照者,入组者均来自淮海地区汉族人群.提取外周血全基因组DNA,应用聚合酶链式反应（polymerase chain reaction,PCR）技术扩增包含多态位点的目的 基因片段,通过琼脂糖凝胶电泳（AGE）检测PCR产物.对PCR产物分别用DNA限制性内切酶NlalV和SmlI进行酶切,用聚丙烯酰胺凝胶电泳（PAGE）、硝酸银染色检测酶切产物,采用聚合酶链式反应-限制性片段长度多态性（restriction fragment length polymorphism,RFLP）技术分析基因型,计算所有研究对象两个SNP位点的基因型频率和等位基因频率.结果 （1）PINK1基因rs45530340位点基因型和等位基因在晚发散发性PD组和正常对照组中的分布无统计学差异（基因型：χ2=1.572,P=0.456;等位基因：χ2=1.318,P=0.251）.（2） LRRK2基因rs1491942 位点基因型和等位基因在晚发散发性PD组与正常对照组中的分布差异有统计学意义（基因型：χ2=6.802,P=0.033;等位基因C：χ2=7.448,P=0.006,OR=1.571,95%CI=1.135~2.176）.结论 （1）PINK1基因rs45530340 多态位点可能不是淮海地区汉族人群晚发散发性PD患者的危险因素.（2）LRRK2基因rs1491942多态位点C等位基因可能是淮海地区汉族人群晚发散发性PD患者的危险因素.     

帕金森病患者PINK1 LRRK2基因单核苷酸多态性分析

目的探讨PINK1基因rs45530340位点及LRRK2基因rs1491942位点单核苷酸多态性(single nucleotide polymorphism,SNP)与淮海地区汉族人群晚发散发性帕金森病(Parkinson’s disease,PD)的相关性。方法收集152例晚发散发性PD患者和160例年龄和性别相匹配的健康对照者,入组者均来自淮海地区汉族人群。提取外周血全基因组DNA,应用聚合酶链式反应(polymerase chain reaction,PCR)技术扩增包含多态位点的目的基因片段,通过琼脂糖凝胶电泳(AGE)检测PCR产物。对PCR产物分别用DNA限制性内切酶NlalV和SmlI进行酶切,用聚丙烯酰胺凝胶电泳(PAGE)、硝酸银染色检测酶切产物,采用聚合酶链式反应-限制性片段长度多态性(restriction fragment length polymorphism,RFLP)技术分析基因型,计算所有研究对象两个SNP位点的基因型频率和等位基因频率。结果 (1)PINK1基因rs45530340位点基因型和等位基因在晚发散发性PD组和正常对照组中的分布无统计学差异(基因型:χ2=1.572,P=0.456;等位基因:χ2=1.318,P=0.251)。(2)LRRK2基因rs1491942位点基因型和等位基因在晚发散发性PD组与正常对照组中的分布差异有统计学意义(基因型:χ2=6.802,P=0.033;等位基因C:χ2=7.448,P=0.006,OR=1.571,95%CI=1.135~2.176)。结论 (1)PINK1基因rs45530340多态位点可能不是淮海地区汉族人群晚发散发性PD患者的危险因素。(2)LRRK2基因rs1491942多态位点C等位基因可能是淮海地区汉族人群晚发散发性PD患者的危险因素。     

湖南地区汉族人群Per2基因多态性与睡眠癫痫的相关性研究

目的探讨Per2C111G基因多态性与中国湖南地区汉族人群睡眠癫痫的关系。方法选取湖南地区汉族癫痫患者300例及健康对照组100例,癫痫患者按好发时间分为觉醒癫痫组、不定期癫痫组、睡眠癫痫组。采用聚合酶链反应(PCR)和基因测序方法检测Per2基因C111G位点的多态性。结果湖南地区汉族人群中,Per2基因C111G多态位点的基因型频率分别为:CC型87.0%、CG型13.0%、GG型0.0%,等位基因C和G频率分别为93.5%和6.5%。癫痫组和对照组间基因型及等位基因型频率差异无统计学意义(P>0.05)。3个癫痫亚组间基因型及等位基因型频率差异亦无统计学意义(P>0.05)。结论 Per2基因C111G位点多态性可能与湖南地区汉族人群睡眠癫痫无关。     

低硒可能导致老年人群认知功能低下：一项队列研究

背景：诸多研究表明,微量元素与人类认知功能密切相关,有关环境硒水平可否以延缓老年人群认知功能下降仍具有争议,更缺乏相应的流行病学调查依据。 目的：探讨环境硒水平与老年人群认知功能的相关性,揭示不同硒水平对老年人认知功能的影响。 设计、时间与地点：采用分层抽样的方法获取研究对象,于2005年在山东省环境硒水平相对不同的潍坊市的高密市与淄博市的淄川区进行相关的采样和调查。 材料：在高密市与淄川区现场,按照分层抽样的方法分别在每个现场随机抽取终身居住于当地的≥65岁的老年人500人,两地共1000例。 方法：采用面对面的问卷调查获得老年人群认知功能的资料,采集环境和人体样品通过检测硒含量分析与人群认知能力之间的相关性。 主要指标：认知评定应用社区痴呆筛查量表(CSID)、美国老年痴呆症登记联盟(CERAD)的词表学习测试、CERAD词表记忆测试、美国印第安纳大学（IU）的故事记忆测试、动物流畅性测验进行现场采访评定。食物、土壤等环境样品以及指甲、静脉血等人体样品,应用荧光分光光度法检测硒含量。 结果：硒摄入量指甲硒、及血硒之间存在正相关性（P<0.001);认知功能评定除动物名词叙述测试外,不同硒水平间认知功能记分的差异均具有统计学意义(P<0.05);剔除可能混杂因素的影响后,硒水平与认知功能间具有明显的正相关性(P<0.05)。并存在剂量-效应关系。 结论：由于该研究的老年人群终身居住于同一地区,硒水平反映终身暴露水平,因此有助于确定硒在人体的生物效应。山东农村老年人群稳定的硒暴露水平研究,支持终身低硒水平与低认知能力相关假设。     

Genetic analysis of the fused in sarcoma gene in Chinese Han patients with Parkinson's disease

Background and purposeExome sequencing in a large essential tremor (ET) family identified a novel nonsense mutation (p.Q290X) in the fused in sarcoma gene (FUS) as the cause of this family. Because of the clinical overlap between ET and Parkinson's disease (PD), the role of FUS in an independent cohort of PD patients from China mainland was evaluated.MethodsThe entire coding region of FUS in 508 Chinese Han patients with PD and the identified variants in 633 normal controls were evaluated. A variant was further screened in an additional 382 controls for the frequency in our population.ResultsA novel variant c.696C > T (p.Y232Y) in 2 sporadic patients with PD and six variants (c.52C > A, p.P18T; c.52C > T, p.P18S; c.147C > A, p.G49G; c.291C > T, p.Y97Y; c.684C > T, p.G228G; c.1176G > A, p.M392I) without significant difference in genotypic and allelic distributions in our PD cohort were identified.ConclusionThe FUS gene is not a genetic risk factor for PD in the population of Chinese Han ethnicity.     

Recreational physical activity and risk of Parkinson's disease

The purpose of this study was to investigate associations between recreational physical activity and Parkinson's disease (PD) risk. We prospectively followed 143,325 participants in the Cancer Prevention Study II Nutrition Cohort from 1992 to 2001 (mean age at baseline = 63). Recreational physical activity was estimated at baseline from the reported number of hours per week on average spent performing light intensity activities (walking, dancing) and moderate to vigorous intensity activities (jogging/running, lap swimming, tennis/racquetball, bicycling/stationary bike, aerobics/calisthenics). Incident cases of PD (n = 413) were confirmed by treating physicians and medical record review. Relative risks (RR) were estimated using proportional hazards models, adjusting for age, gender, smoking, and other risk factors. Risk of PD declined in the highest categories of baseline recreational activity. The RR comparing the highest category of total recreational activity (men ≥ 23 metabolic equivalent task‐hours/week [MET‐h/wk], women ≥ 18.5 MET‐h/wk) to no activity was 0.8 (95% CI: 0.6, 1.2; P trend = 0.07). When light activity and moderate to vigorous activity were examined separately, only the latter was found to be associated with PD risk. The RR comparing the highest category of moderate to vigorous activity (men ≥ 16 MET‐h/wk, women ≥ 11.5 MET‐h/wk) to the lowest (0 MET‐h/wk) was 0.6 (95% CI: 0.4, 1.0; P trend = 0.02). These results did not differ significantly by gender. The results were similar when we excluded cases with symptom onset in the first 4 years of follow‐up. Our results may be explained either by a reduction in PD risk through moderate to vigorous activity, or by decreased baseline recreational activity due to preclinical PD. © 2007 Movement Disorder Society     

Incidence of mutations in the PARK2, PINK1, PARK7 genes in Polish early-onset Parkinson disease patients

Background and purposeParkinson disease (PD) is a complex disease, comprising genetic and environmental factors. Despite the vast majority of sporadic cases, three genes, i.e. PARK2, PINK1 and PARK7 (DJ-1), have been identified as responsible for the autosomal recessive form of early-onset Parkinson disease (EO-PD). Identified changes of these genes are homozygous or compound heterozygous mutations. The frequency of PARK2, PINK1 and PARK7 mutations is still under debate, as is the significance and pathogenicity of the single heterozygous mutations/variants, which are also detected among PD patients. The aim of the study was to analyze the incidence of autosomal recessive genes PARK2, PINK1, PARK7 mutations in Polish EO-PD patients.Material and methodsThe analysis of the PARK2, PINK1 and PARK7 genes was performed in a group of 150 Polish EO-PD patients (age of onset < 45 years). Mutation analysis was based on sequencing and gene dosage abnormality identification.ResultsMutations were identified only in the PARK2 and PINK1 genes with the frequency of 4.7% and 2.7% of subjects, respectively. In PARK2, point mutations and exons' rearrangements, and in PINK1 only missense mutations were detected. In both genes mutations were found as compound heterozygous/homozygous and single heterozygous. EO-PD patients’ genotype-phenotype correlation revealed similarities of clinical features in mutation carriers and non-carriers.ConclusionsThe frequency of the PARK2, PINK1, PARK7 mutations among Polish EO-PD patients seems to be low. The role of single heterozygous mutations remains a matter of debate and needs further investigations.     

Rate of cognitive decline in premotor Parkinson's disease: A prospective study (NEDICES)

Previous research has documented cognitive impairment in the early stages of Parkinson's disease (PD). It is not known when this decline starts or if decline progresses at an accelerated rate during the premotor period of the disorder. In this population‐based prospective study of older people (≥65 years) from the Neurological Disorders in Central Spain (NEDICES) cohort, we compared the rates of cognitive decline in 3 groups: (1) non‐PD elderly controls; (2) prevalent PD patients (those diagnosed with the disease at baseline, 1994–95); and (3) premotor PD subjects (those diagnosed with the disease at follow up, 1997–98, but not at baseline). A 37‐item version of the Mini–Mental State Examination (37‐MMSE) was administered in the 2 visits of the study. From 2487 participants (age, 72.8 ± 6.0 years), including 2429 controls, we recruited 21 premotor PD cases, and 37 prevalent PD cases. At baseline, the mean 37‐MMSE score was 28.5 ± 4.7 in prevalent cases, 28.1 ± 4.6 in premotor cases, and 29.9 ± 5.0 in controls (P = .046). During the 3‐year follow‐up period, there was a significant score decline of 2.4 ± 4.6 points in prevalent cases versus 0.2 ± 4.1 points in premotor cases and 0.3 ± 4.0 points in controls (Kruskal–Wallis test, P = .03). In the NEDICES cohort, cognitive test scores of prevalent PD cases declined at a rate above and beyond that observed in premotor PD cases and in controls. The rate of cognitive decline in premotor PD and controls was similar. Our data suggest that a decline in global cognitive function does not occur in premotor PD. © 2012 Movement Disorder Society     

丝裂酶原活化蛋白激酶1基因多态性与中国汉族阿尔茨海默病的关联研究

目的:研究探讨丝裂酶原活化蛋白激酶1(MAPK1)基因在中国汉族阿尔茨海默病(AD)发生过程中的作用。方法:根据《美国精神障碍诊断和统计手册》(DSM-IV)和美国国立神经病、语言功能紊乱和脑卒中研究所及AD和相关疾病协会临床诊断标准(NINCDS-ADRDA),收集中国东部和西南部人群AD患者715例和健康对照者760人。选取MAPK1基因3个标签多态性位点rs2276006、rs1063311和rs2006893。采用SNa Pshot SNP分型技术对这3个SNP位点进行分析。结果:中国东部和西南部人群AD组与对照组间MAPK1基因各位点基因多态性及等位基因分布频率差异无统计学意义(P0.05);东部及西南部人群合并后AD组与对照组间MAPK1基因各位点基因多态性及等位基因分布频率差异无统计学意义(P0.05),连锁不平衡检验显示各SNP位点之间存在强连锁(D'0.95),单体型分析结果显示病例组与对照组间单体型估计频率差异无统计学意义(P0.05)。结论:MAPK1基因可能不是中国汉族AD的主要致病基因。