单胺氧化酶B基因多态与早发帕金森病的相关性

Objective To investigate the association between polymorphisms in monoamine oxidase B (MAO-B)and early-onset Parkinson's disease(EOPD).Methods Polymerase chsin reactionrestriction fragment length polymorphism was used to identify the genotypes of polymorphisms in MAO-B in 65 patients in EOPD group(early-onset age<50 years),60 in late-onset Parkinson's disease(LOPD) group(late-onset age≥160 years)and 66 healthy controls(<50 years).Results The frequency of AA genotype was higher in EOPD groups(49/65,75.4%)than in healthy controls(34/66,51.5%),and the difference between them was statistically significant(x2=8.075,P=0.018).The frequency of AA genotype between EOPD group and LOPD group,between LOPD group and healthy controls had no statistical significance.The frequency of AA genotype between male in EOPD group and male healthy controls,between female in EOPD group and female healthy controls had no statistical significance.The frequencies of AA genotype between male in EOPD group and LOPD group,between female in EOPD group and in LOPD group had no statistical significance.The frequency of AA genotype between male in LOPD group and in healthy controls,between female in LOPD group and female healthy controls had no statistical significance.The frequency of A alleles was higher in EOPD group(107/130,82.3%)than in healthy controls(87/132,65.9%)and the difierence between them was statistical significant(x2=9.165,P=0.002).The frequency of A allele between EOPD group and LOPD group,between LOPD group and healthy controls had no statistical significance. The frequency of A allele was higher in male EOPD group (60/70,85.7%) than in male healthy controls(51/72,70. 8% ), the difference between them was statistically significant (X2 =4. 606, P=0. 032) ;the frequency of A alleles was higher in female in EOPD group (47/60,78. 3% ) than in female healthy controls(36/60,60. 0% ), the difference between them was statistical significance( x2 =4. 728, P = 0. 030). The frequency of A alleles between male EOPD group and male LOPD group, between female EOPD group and female LOPD group had no statistical significance. The frequency of A allele between male LOPD group and male healthy controls, between female LOPD group and female healthy controls had no statistical significance. Conclusions The AA genotype of MAO-B is the risk factor of EOPD. The A allele of MAO-B is a risk factor of EOPD group for both male and female.     

单胺氧化酶B基因多态与早发帕金森病的相关性

Objective To investigate the association between polymorphisms in monoamine oxidase B (MAO-B)and early-onset Parkinson's disease(EOPD).Methods Polymerase chsin reactionrestriction fragment length polymorphism was used to identify the genotypes of polymorphisms in MAO-B in 65 patients in EOPD group(early-onset age<50 years),60 in late-onset Parkinson's disease(LOPD) group(late-onset age≥160 years)and 66 healthy controls(<50 years).Results The frequency of AA genotype was higher in EOPD groups(49/65,75.4%)than in healthy controls(34/66,51.5%),and the difference between them was statistically significant(x2=8.075,P=0.018).The frequency of AA genotype between EOPD group and LOPD group,between LOPD group and healthy controls had no statistical significance.The frequency of AA genotype between male in EOPD group and male healthy controls,between female in EOPD group and female healthy controls had no statistical significance.The frequencies of AA genotype between male in EOPD group and LOPD group,between female in EOPD group and in LOPD group had no statistical significance.The frequency of AA genotype between male in LOPD group and in healthy controls,between female in LOPD group and female healthy controls had no statistical significance.The frequency of A alleles was higher in EOPD group(107/130,82.3%)than in healthy controls(87/132,65.9%)and the difierence between them was statistical significant(x2=9.165,P=0.002).The frequency of A allele between EOPD group and LOPD group,between LOPD group and healthy controls had no statistical significance. The frequency of A allele was higher in male EOPD group (60/70,85.7%) than in male healthy controls(51/72,70. 8% ), the difference between them was statistically significant (X2 =4. 606, P=0. 032) ;the frequency of A alleles was higher in female in EOPD group (47/60,78. 3% ) than in female healthy controls(36/60,60. 0% ), the difference between them was statistical significance( x2 =4. 728, P = 0. 030). The frequency of A alleles between male EOPD group and male LOPD group, between female EOPD group and female LOPD group had no statistical significance. The frequency of A allele between male LOPD group and male healthy controls, between female LOPD group and female healthy controls had no statistical significance. Conclusions The AA genotype of MAO-B is the risk factor of EOPD. The A allele of MAO-B is a risk factor of EOPD group for both male and female.     

中国人群单胺氧化酶-B基因多态性与帕金森病相关性研究

目的 探讨人多巴胺代谢酶—单胺氧化酶B(MAO—B)基因内含子13内核苷酸A／G多态性与帕金森病(Parkinson’s disease，PD)遗传易患性的关系。方法 利用聚合酶链反应—变性高压液相技术(PCR—DHPLC)分析了MAO—B基因13内含子A／G多态性在PD患者与健康对照之问分布频率的差异。结果 野生基因型(A或AA)在总体PD或对照组中的分布频率77．8％和74．0％，杂合基因型A／G的频率分别为11．7％和8．4％；突变基因型(G／G或G)分别为10．5％和17．5％，使患PD的危险度降低1．8倍(P=0．04)；按发病年龄分组，突变基因型使患者早发PD的危险度降低2．4倍(P=0．031)。无论从总体分析，还是按发病年龄或性别分组，等位基因在各个组的分布频率差异无显著意义。结论 MAO—B的A／A(A)基因型是PD发生的危险因素，与PD的遗传易患性有关，对早发PD影响较大。     

中国人单胺氧化酶-A基因的EcoRV酶切位点多态性与帕金森病的相关性

目的：探讨多巴胺代谢酶—单胺氧化酶-A基因EcoRV酶切位点多态性与帕金森病(Parkinsondisease，PD)遗传易感性的关系。方法：选择PD病人287例(包括发病年龄小于等于50岁的早发型PD和发病年龄大于50岁的晚发型PD)和正常对照164例，利用PCR-RFLP技术分析了单胺氧化酶-A(MAO-A)EcoRV酶切位点多态性在PD病人与正常对照之间分布频率的差异。结果：MAO-A基因EcoRV酶切位点在总体对照组和总体PD病人之间的分布没有显著差异；根据发病年龄分组后，不管是早发PD病人还是晚发PD病人，与对照组相比等位基因和基因型频率均无显著性差别。按性别分组后发现，男性PD和对照组的基因型频率或是等位基因频率存在显著性差异。结论：研究结果支持MAO-A基因多态性与PD相关的假说，而且表明此关系与PD发病年龄和性别有关。     

单胺氧化酶B基因13内含子G/A多态性与帕金森病的关系

目的探讨多巴胺代谢酶———单胺氧化酶B(MAO-B)基因13内含子G/A多态性与帕金森病(PD)的关系。方法应用PCR-限制性片段长度多态性(RFLP)技术检测166例PD患者(其中早发型52例,晚发型114例)和170名正常对照者的MAO-B基因13内含子G/A位点的基因型和等位基因,比较分析其分布情况。结果 PD组与正常对照组MAO-B基因野生型(AA)、杂合型(AG)、突变型(GG)频率及等位基因频率差异无统计学意义;PD早发型亚组的AA型(80.8%)和A等位基因型频率(86.5%)显著高于晚发型亚组(60.5%,71.5%)及正常对照组(60.6%,71.5%)(均P<0.05);PD晚发型亚组与正常对照组各基因型和等位基因频率的差异无统计学意义;PD男性及女性亚组与同性别正常对照组的基因型和等位基因频率的差异均无统计学意义。结论 MAO-B基因13内含子AA型和A等位基因频率增高是PD发病的危险因素之一;MAO-B基因13内含子G/A多态性与PD,尤其是与早发型PD的遗传易感性有关。     

单胺氧化酶B基因微卫星多态与帕金森病的相关分析

目的 研究上海地区汉族人群中单胺氧化酶B(MAOB)基因第二内含子中鸟嘌呤、胸腺嘧啶(GT)二碱基重复的微卫星多态位点与帕金森病(Parkinson’s disease，PD)易患性之间的关系。方法 采用扩增片段长度多态法(Amp—FLP)，在上海汉族人群中选择67例散发PD患者为PD组和204名健康者为对照组，运用微卫星荧光标记—半自动基因分型技术精确计算出微卫星等位基因片段大小，进而分析该多态在PD易患性中的作用。结果 该位点短片段(≤170bp)等位基因的分布在：PD组中明显高于与对照组(x^2=11．28，P=0．001)，而172bp等位基因在PD组中亦明显低于与对照组(x^2=5．16，P=0．023)。结论 MAOB基因GT二碱基重复多态位点与本组PD患者的易患性有关。     

中国人单胺氧化酶-A基因的EcoRV酶切位点多态性与帕金森病的相关性

目的:探讨多巴胺代谢酶一单胺氧化酶-A基因EcoRV酶切位点多态性与帕金森病(Parkinson disease,PD)遗传易感性的关系.方法:选择PD病人287例(包括发病年龄小于等于50岁的早发型PD和发病年龄大于50岁的晚发型PD)和正常对照164例,利用PCR-RFLP技术分析了单胺氧化酶-A(MAO-A)EcoRV酶切位点多态性在PD病人与正常对照之间分布频率的差异.结果:MAO-A基因EcoRV酶切位点在总体对照组和总体PD病人之间的分布没有显著差异;根据发病年龄分组后,不管是早发PD病人还是晚发PD病人,与对照组相比等位基因和基因型频率均无显著性差别.按性别分组后发现,男性PD和对照组的基因型频率或是等位基因频率存在显著性差异.结论:研究结果支持MAO-A基因多态性与PD相关的假说,而且表明此关系与PD发病年龄和性别有关.     

单胺氧化酶B抑制剂在治疗帕金森病中的研究

理想的帕金森病治疗药物应是既能缓解症状，又能减缓疾病的进展。Safinamide是一种新型单胺氧化酶B（MAO-B）抑制剂，目前正在用于抗痉挛、抗帕金森病和神经保护方面的研究。Safmamide具有独特的分子结构、多重作用机制和很高的治疗指数。它既能高效、选择性和可逆的抑制MAO-B的活性，又能阻断钠、钙通道和抑制谷氨酸的释放。Safinamide还具有极好的的生物利用度、线型动力学、较长的半衰期和良好的安全性及耐受性。本文对主要的MAO-B抑制剂作一介绍。     

新疆地区维吾尔族、汉族单胺氧化酶B基因多态性与帕金森病的相关性研究

目的探讨中国新疆地区维吾尔族、汉族人群多巴胺代谢酶-单胺氧化酶B(MAO-B)基因内含子13 G/A多态性与帕金森病(PD)遗传易感性的关系,以及PD患者基因型与临床特点的关系。方法研究对象为中国新疆地区241例PD患者(PD组),其中维吾尔族95例(维吾尔族PD组)、汉族146例(汉族PD组);另选择247名健康对照者(对照组),其中维吾尔族104例、汉族143例。收集并分析PD患者临床资料;采用聚合酶链反应-限制性片段长度多态性分析法(PCR-RLFP)进行MAO-B基因多态性分析,研究基因型和等位基因频率分布情况。结果①PD组与对照组MAO-B基因G/A基因型及等位基因频率差异无统计学意义。②维吾尔族PD组和汉族PD组与对照组的基因型及等位基因频率差异无统计学意义。③男性PD组和女性PD组与相同性别对照组的基因型及等位基因频率分布差异无统计学意义。④发病年龄≤70岁PD患者与对照组基因型频率、等位基因频率差异无统计学意义;>70岁的PD患者与对照组基因型频率、等位基因频率差异有统计学意义。⑤新疆地区维吾尔族、汉族PD患者的3种基因型的临床特点差异无统计学意义。结论MAO-B基因的AA基因型与A等位基因频率增高是发病年龄>70岁新疆维吾尔族和汉族PD患者的危险因素。PD患者MAO-B基因3种基因型的临床特点无差别。     

COMT基因rs4680位点与中国汉族人群帕金森病遗传易患性关联性分析

目的 探讨儿茶酚胺氧位甲基转移酶(COMT)基因rs4680位点Val158Met多态性与帕金森病遗传易患性的相关性.方法 采用聚合酶链反应-连接酶检测反应(polymerase chain reaction-ligase detection reaction,PCR-LDR)基因多态性测序方法,分析COMT rs4680位点基因型及等位基因频率在帕金森病患者(437例)和健康对照者(530人)间的分布差异.结果 帕金森病患者G等位基因频率为77.2％,A等位基因频率为22.8％,而在健康对照者分别为74.7％、25.3％,两组间COMTrs4680位点Val158Met等位基因频率分布差异没有统计学意义(P =0.199).各基因型频率在帕金森病患者分别为G/G型57.4％、G/A型39.6％、A/A型3.0％,在健康对照者分别为54.9％、39.6％、5.5％,两组间基因型频率分布差异无统计学意义(P=0.156).在校正性别、年龄混杂因素后经二元Logistic回归分析,COMT rs4680位点各基因型与帕金森病发病风险之间仍无相关性.结论 COMT基因r4680位点Val158Met多态性与中国汉族人群帕金森病易患性可能无关,进一步扩大样本量及在其他不同种族中的研究能更好地确定COMT rs4680位点Val158Met多态性在帕金森病发病风险中的作用.     

Endogenous urinary monoamine oxidase inhibitor excretion in Parkinson's disease and other neurological disorders

Summary In this study, urinary output of both neutral (tribulin) and basic monoamine oxidase inhibitory activity was measured in parkinsonian patients, other neurological patients and controls. No significant differences in output were found between these different groups. In general, tribulin output rose with age, in parallel with known changes in monoamine oxidase B activity.     

MDL 72,974: a potent and selective enzyme-activated irreversible inhibitor of monoamine oxidase type B with potential for use in Parkinson's disease

Summary MDL 72,974, (E)-2-(4-fluorophenethyl)-3-fluoroallylamine, was designed to be a selective inhibitor of monoamine oxidase type B (MAO-B). In vitro, the compound inhibits rat brain mitochondrial MAO in a concentration and time-dependent fashion and shows marked selectivity for the B form (IC₅₀=680 and 3.6nM for MAO-A and MAO-B, respectively). After oral administration to rats, the compound shows preferential inhibition of brain MAO-B with ED₅₀ values of 8 and 0.18 mg/kg p.o. for the A and B forms, respectively. Selectivity is retained on repeat dosing. MDL 72,974 did not significantly potentiate the cardiovascular effects of intraduodenually-administered tyramine in anaesthetized rats and had only minor indirect sympathominatic effects in the pithed rat. At MAO-B selective doses the neurotoxic effect of MPTP in mice was blocked.Part of this work was presented at the 7th European Winter Conference on Brain Research (Zreika et al., 1987).     

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.     

环指蛋白213基因多态性与中国汉族成人型烟雾病遗传易患性的相关性

目的 探讨环指蛋白213(RNF213)基因rs112735431和rs138130613两位点多态性与中国汉族成人型烟雾病的遗传易患性的关系.方法 从南京卒中注册系统中提取2010年12月至2011年10月经脑血管造影明确诊断的64例成年型烟雾病患者,同时选取96名性别和年龄与烟雾病患者相匹配的健康人作为对照.通过改进的多重连接酶检测反应技术分析RNF213基因rs112735431和rs138130613位点的多态性,对各位点基因型、等位基因型频率进行比较分析.结果 病例组中rs112735431位点GA+AA基因型频率为10.94％(7/64)、GG基因型频率为89.06％(57/64),等位基因A频率为6.25％ (8/128)、等位基因G频率为93.75％ (120/128);对照组分别为1.04％(1/96)、98.96％(95/96),0.52％ (1/192)、99.48％ (191/192),两组间差异具有统计学意义(OR=11.67,95％ CI 1.40 ～97.28,P =0.007;OR=12.73,95％ CI 1.57 ～ 103.09,P=0.003).rs138130613位点的基因型和等位基因频率在两组间差异无统计学意义.结论 RNF213基因rs112735431位点的多态性可能是中国汉族成人型烟雾病患者的易患因子.