中国汉族人群SLC6A11基因多态性与耐药性癫痫的相关性研究

目的探索中国汉族人群SLC6A11基因多态性与耐药性癫痫的相关性。方法据入选标准和排除标准收集在湘雅医院门诊的480例癫痫患者,应用Illumina Golden Gate定制芯片对288例药物敏感癫痫患者和192例药物耐药癫痫患者进行SLC6A11基因型鉴定,分析单位点基因型频率和单体型与耐药性癫痫的相关性。结果敏感组与耐药组之间SLC6 A11基因14个SNP位点的基因型频率差异无统计学意义(P0.05);耐药性癫痫患者单倍型5的频率高于敏感组(1%vs.4%;OR=2.56[0.107-0.763];P=0.01),经过Bonferroni多重检验后单倍型5的频率在两组间无显著差异。结论 SLC6A11基因的14个SNP多态性可能与中国汉族人群的癫痫耐药性无关。     

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...     

SLC25A12基因多态性与孤独性障碍的关联

目的：探讨SLC25A12基因单核苷酸多态性（SNP）与孤独性障碍的遗传关联性。方法：采用聚合酶链式反应和DNA芯片杂交技术,在124个汉族孤独性障碍患儿核心家系中,检测了SLC25A12基因的2个SNP位点（rs2056202,rs2292813）,采用传递不平衡检验（TDT）和单倍型的方法进行关联分析。结果：在124个患儿核心家系中,所测得的2个SNP位点的等位基因和基因型的频数分布均符合Hardy-Weinberg平衡检验（χ^2=0.009,P=0.92;χ^2=0.006,P=0.94）。而且这2个SNP处于一个强连锁不平衡区域（D’=0.842,r2=0.566）。对124个核心家系TDT检验,发现带有杂合子基因的父代优先传递给子代的等位基因的传递率和此传递率的置信区间差异无显著性（P〉0.05）;所有样本的2个SNP位点,未发现与孤独性障碍的显著关联。结论：SLC25A12基因可能不是这些汉族家庭儿童孤独性障碍的主要易感基因。     

囊泡单胺转运蛋白2基因多态性与帕金森病患者抑郁状态相关性的研究

目的 研究囊泡单胺转运蛋白2（VMAT2）的rs363371和rs363324基因多态性与汉族人群中PD患者合并抑郁状态的相关性。方法 收集102例汉族帕金森病（PD）患者,通过采用17项汉密尔顿抑郁量表（HAMD-17）将患者分为PD合并抑郁组和PD未合并抑郁组,用连接酶法对VMAT2的rs363371和rs363324进行了基因型分型,运用二元Logistic回归检验分析PD患者合并抑郁的危险因素。结果 rs363371的AA基因型降低了PD患者合并抑郁的风险（OR=0.22,59%CI 0.07-0.75,P=0.015）。UP3的高分值增加了PD患者合并抑郁的风险（OR=1.08,59%CI 1.02-1.15,P=0.009）。较长的病程增加了PD患者合并抑郁的风险（OR=1.15,59%CI 1.01-1.31,P=0.038）。rs363324的基因多态性并未增加PD合并抑郁的风险。结论 VMAT2的rs363371的AA基因型降低了汉族人群PD患者合并抑郁的风险。     

有自杀意念的儿童青少年双相障碍抑郁发作患者SLC6A4 基因甲基化研究

目的 探讨儿童青少年双相障碍（PBD）抑郁发作患者自杀意念与SLC6A4基因甲基化 的关系。方法 选取 2020 年 12 月至 2022 年 12 月于新疆维吾尔自治区人民医院临床心理科住院的 43 例 PBD 抑郁发作患者为研究对象。采用自杀意念自评量表（SIOSS）评估患者的自杀意念，将总分≥ 12 分且掩饰因子得分＜ 4 分的患者纳入有自杀意念组（n=29），将总分＜ 12 分的患者纳入无自杀意念组 （n=14）。采用 Methprimer 软件对SLC6A4基因启动子区进行甲基化岛预测和甲基化引物设计，将提取好 的DNA经亚硫酸盐转化后进行PCR扩增和焦磷酸盐测序，确定甲基化的CpG位点和甲基化率。比较两组 患者SLC6A4基因不同位点甲基化的差异，采用 Spearman 相关分析基因甲基化与自杀意念的相关性。 结果 基因甲基化检测结果显示，两组患者SLC6A4基因甲基化的位点包括 CpG1、CpG2.3、CpG4、 CpG5.6位点。有自杀意念组与无自杀意念组患者CpG1、CpG2.3、CpG4位点的基因甲基化率比较［48.28% （14/29）比 8/14、96.55%（28/29）比 14/14、20.69%（6/29）比 6/14］，差异无统计学意义（χ2 =0.297、0.494、2.306； P＞ 0.05）。有自杀意念组患者的 CpG5.6 位点基因甲基化率高于无自杀意念组［68.97%（20/29）比 5/14］， 差异有统计学意义（χ2 =4.289，P＜ 0.05）。相关分析结果显示，PBD 抑郁发作患者的 SIOSS 得分与 SLC6A4基因甲基化CpG1位点、CpG2.3位点、CpG4位点不存在相关性（r=-0.244、-0.210、-0.281；P＞0.05）； 与甲基化 CpG5.6 位点呈正相关（r=0.312，P＜ 0.05）。结论 PBD 抑郁发作患者的自杀意念与SLC6A4基 因甲基化 CpG5.6 位点有关，为明确其自杀意念的发生原因提供了基础。     

SORL1基因多态性与中国东北地区帕金森病的相关性分析

目的探究SORL1基因rs2070045位点的单核苷酸多态性与帕金森病(Parkinson disease,PD)的相关性。方法本研究纳入215名中国东北地区汉族健康人和377例PD患者。根据其发病年龄,将PD组患者再分为早发PD组(发病年龄≤50岁)和晚发PD组(发病年龄50岁),收集一般临床资料,提取外周血基因组DNA,利用MALDI-TOF-PEX技术检测SORL1基因rs2070045多态性分布情况,分析其与帕金森病的相关性。结果在PD组与对照组以及晚发PD组与对照组的比较中,SORL1基因rs2070045位点单核苷酸多态性的基因型及等位基因频率分布无统计学差异。早发PD组与对照组比较,rs2070045基因型分布有显著差异(P=0.036),而等位基因频率无显著差异。在晚发PD中G等位基因携带者的起病年龄明显低于非携带者(P=0.001),其他临床特征如性别、Hoehn-Yahr分期以及病程在携带者和非携带者间无统计学差异。结论 SORL1基因rs2070045位点的单核苷酸多态性与中国东北地区汉族早发帕金森病相关,G等位基因可能是早发PD的保护性因素。     

PITX3基因多态性与帕金森病相关性的研究进展

PITX3基因是垂体同源盒基因家族的成员之一,其表达产物在中脑黑质多巴胺(DA)能神经元终末分化和生存维持中起关键作用。诸多研究表明PITX3单核苷酸多态性(SNP)与帕金森病(PD)有关。已经报道的PITX3基因有三个SNP位点,分别为rs2281983、rs4919621和rs3758549,有学者认为PITX3基因rs3758549基因的多态可能是PD的危险因素,但也有研究认为两者并无关联。而多项研究证实PITX3基因rs2281983和rs4919621的基因多态性不是PD的危险因素。     

新疆地区帕金森病遗传易感性与COMT和CYP1A1基因多态性相互关系的研究

目的探讨儿茶酚胺氧位甲基转移酶(catechol-O-methyltransferase,COMT)基因G1947A多态性和细胞色素P450 1A1(cytochrome P4501A1,CYP 1A1)基因Msp I多态的独立及其协同作用与新疆地区帕金森病(Parkinson’s disease,PD)遗传易感性的关系。方法应用聚合酶链反应-限制性片段长度多态性分析法(PCRRFLP)分析新疆地区237例散发性PD患者和247例健康对照者的COMT基因G1947A多态性、CYP 1A1基因Msp I多态性。结果 (1)COMT基因G1947A多态性、CYP 1A1基因Msp I多态性分布在PD组与对照组间无统计学差异(均P>0.05)。均按民族、性别、年龄分层后,两种基因的多态性分布在各亚组PD组和对照组间无统计学差异(均P>0.05)。(2)COMT G/G基因型和CYP 1A1 T/T基因型间的协同作用可使新疆维吾尔族人群中PD的发生风险增加3.288倍(OR=3.288)。(3)COMT G/G基因型与CYP 1A1 T/C基因型间的协同作用可分别使新疆维吾尔族人群中、年龄≥60岁人群中PD的发生风险下降0.245倍、0.451倍(维吾尔族人群:OR=0.245、年龄≥60岁人群:OR=0.451)。结论 COMT基因、CYP 1A1基因不同基因型间的协同作用可增加或减少新疆地区部分人群PD的发生风险。     

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.     

Omi/Htra2基因1195G/A多态性与帕金森病的相关性研究

目的 探讨中国汉族人群Omi/Htra2基因编码区1195G/A 位点的单核苷酸多态性(SNP)与帕金森病(PD)发病的关系.方法 采用聚合酶链反应-限制性酶切片段长度多态性(PCR-RFLP)技术,检测56例PD患者和109例健康人的Omi/Htra2基因编码区1195G/A位点多态性的基因型及等位基因频率.结果 56例PD病例中Omi/Htra2基因1195G/G基因型55例,G/A杂合子1例;对照组中109例全部为G/G基因型.结论 中国汉族人群Omi/Htra2基因编码区1195G/A杂合子可能是PD的患病因素.     

Lack of association between CYP1A1 polymorphism and Parkinson's disease in a Chinese population

Summary. Apart from very few families who have a direct cause from genetic mutation, causes of most Parkinson's disease (PD) remain unclear. Many allelic association studies on polymorphism of different candidate genes have been studied. Although these association studies do not imply a causal relationship, it does warrant further studies to elucidate the pathophysiologic significance. CYP1A1 polymorphisms have been reported to be associated with PD in a Japanese population sample. Since CYP1A1 transforms aromatic hydrocarbons into products that may be neurotoxic and perhaps lead to PD, we therefore undertook a study to look at the possible association of CYP1A1 polymorphism and PD in a Chinese population. Contrary to the Japanese result, we did not find any statistically significant difference between the PD group and the control group in our study with a bigger sample size. Received April 30, 2001; accepted September 4, 2001     

SLC26A4 gene polymorphism and late-onset Alzheimer’s disease in a Han Chinese population from Qingdao,China

In a recent genome-wide association study,the SLC26A4 gene rs2072064 polymorphism was found to be associated with late-onset Alzheimer’s disease in Caucasians.Here,we investigated this association in a large Northern Han Chinese cohort consisting of 599 sporadic late-onset Alzheimer’s disease patients and 598 healthy controls matched for sex and age in a Northern Han Chinese population from Qingdao,China.Genotyping by the polymerase chain reaction-ligase detection reaction revealed that there were significant differences in the genotype (P=0.017) and allele (P=0.007) frequencies of the rs2072064 polymorphism between late-onset Alzheimer’s disease patients and controls.The A allele of this polymorphism was significantly associated with a reduced risk of late-onset Alzheimer’s disease (odds ratio (OR)=0.792,95% confidence interval (CI)=0.670-0.937,P=0.007).When the data were stratified by the apolipoprotein E ε4 status,there was a significant difference only among apolipoprotein E ε4 non-carriers (genotypic P=0.001,allelic P=0.001).Furthermore,the association between rs2072064 and late-onset Alzheimer’s disease remained significant by logistic regression analysis after adjustment for age,gender,and the apolipoprotein E ε4 carrier status (dominant model:OR=0.787,95% CI=0.619-1.000,P=0.050;recessive model:OR=0.655,95% CI=0.448-0.959,P=0.030;additive model:OR=0.792,95% CI=0.661-0.950,P=0.012).These findings suggest that SLC26A4 is a susceptibility gene for late-onset Alzheimer’s disease in a Northern Han Chinese population from the Qingdao area.     

Positive association between an estrogen receptor gene polymorphism and Parkinson's disease with dementia

Parkinson's disease (PD) is a common cause of dementia in the elderly. Dementia in Alzheimer's disease (AD) and PD share common biologic and clinical features. The estrogen receptor (ER) gene is one of the susceptibility genes for AD. In order to test the hypothesis that the overlap between AD and PD may have a genetic basis, we determined ER gene polymorphisms in 13 PD patients with dementia (PDD) (age +/- SD; 71.9 +/- 5.5 years), 71 PD patients without dementia (PDND) (68.4 +/- 7.5 years), 86 AD patients (76.8 +/- 8.0 years) and 51 control subjects (CTL) (74.9 +/- 6.9 years). ER genotypes were classified as a P or p allele on the basis of a Pvu II-RFLP, and X and x on the basis of a Xba I-RFLP. The frequency of the P allele in the PDD group as well as the AD group was higher than that in CTL. There was no significant difference in the distribution of the P allele between CTL and PDND. There were no significant differences in the distribution of the X allele among the PDD, PDND and CTL groups, whereas a higher incidence was found in AD. We conclude that the ER gene may be a common susceptibility gene for dementia in PD as well as AD.     

Parkin基因R/W366及V/L380多态性与散发性帕金森病

目的　探讨Parkin基因V/L380及R/W36 6多态性与散发性帕金森病 (PD)的遗传易感性之间的关系。方法　以 12 0例散发性PD患者为研究对象 ,12 0名正常人作为对照。采用聚合酶链式反应 (PCR)扩增所需DNA片段 ,用限制性内切酶酶切技术测定所研究对象的基因型和等位基因。结果　PD组R/W36 6多态性等位基因频率显著低于对照组 (连续校正χ2 =4 0 76 ,P <0 0 5 ) ;而V/L380多态性与女性散发性PD的遗传易感性相关联 (χ2 =4 4 5 ,P =0 0 3,OR =2 4 9) ,与发病年龄不相关。结论　Parkin基因R/W36 6和V/L380多态性可能与散发性PD的遗传易感性相关。     

Lack of association between an estrogen receptor 1 gene polymorphism and Parkinson's disease with dementia

OBJECTIVE: To test for an association between an estrogen receptor 1 (ESR1) gene polymorphism and Parkinson's disease with dementia (PDD) in Finnish subjects. SUBJECTS AND METHODS: Forty-one clinically demented and pathologically confirmed PDD patients and 59 cognitively intact aged individuals with normal neuropathology were genotyped for the ESR1 PvuII polymorphism. RESULTS: We found no significant differences in the genotype or allele frequencies when the PDD patients were compared with the controls. Nor were there any significant differences in these frequencies when the PDD patients with coexisting Alzheimer's disease pathology were compared with the control group. CONCLUSION: We failed to demonstrate an association between dementia-associated PD and the ESR1 PvuII polymorphism in Finnish subjects.     

Serotonin and dopamine transporter genes do not influence depression in Parkinson's disease

Altered levels of the neurotransmitters dopamine and serotonin are observed in both Parkinson's disease (PD) and depression. Therefore, the neurotransmitter transporter genes, SLC6A3 (dopamine) and SLC6A4 (serotonin) are candidates for depression in PD. We genotyped 24 tagging SNPs together with VNTRs and the SLC6A4 LPR polymorphism in 190 PD patients categorised according to lifetime history of depression. Log‐additive, dominant and recessive statistical models were constructed. No significant genotype or haplotype associations were observed suggesting that common genetic variables around the dopamine and serotonin transporter genes do not play a significant role in the etiology of depression in PD. © 2008 Movement Disorder Society     

脑源性神经营养因子和血清素再摄取转运体编码基因甲基化与卒中预后的关系

DNA甲基化与卒中预后相关。脑源性神经营养因子（brain-derived neurotrophic factor,BDNF）基因及血清素再摄取转运体编码基因——溶质载体家族6成员4（solute carrier family 6,member 4,SLC6A4）基因表达均受到DNA甲基化调控,可能通过多种途径在改善卒中患者的临床预后方面发挥重要作用。BDNF基因启动子区域的甲基化会导致BDNF的合成减少,从而通过抑制细胞黏附、细胞增殖、血管生成等多种机制影响卒中后的功能恢复;BDNF基因甲基化与神经可塑性相关,这可能解释其对卒中后康复治疗的影响;BDNF基因甲基化使杏仁核和海马体对恐惧的反射增强,导致卒中患者更容易出现焦虑、抑郁症状。SLC6A4基因启动子区域高甲基化水平可能导致5-羟色胺能轴调节障碍,进而促进大脑和外周血小板聚集和局部血管收缩,增加心脑血管事件的复发风险;SLC6A4基因甲基化可能通过影响运动皮质兴奋性、神经元可塑性以及影响炎症因子和免疫介质的释放,影响卒中后康复;同时可能通过影响海马神经元的可塑性以及犬尿氨酸轴、下丘脑-垂体-肾上腺轴的平衡与卒中后抑郁的发生相关。本文主要通过综述既往相关研究,重点介绍BDNF和SLC6A4基因甲基化对卒中预后的影响以及可能的作用机制。     

CYP2D6*4 polymorphism is not associated with Parkinson's disease and has no protective role against Alzheimer's disease in the Korean population

CYP2D6*4 polymorphism is reported to be associated with Parkinson's disease (PD) and to have protective role against Alzheimer's disease (AD). Such findings are not extensively studied in the Oriental population, especially Koreans. The effects of CYP2D6*4 polymorphism on AD and PD were investigated by polymerase chain reaction-restriction fragment length polymorphism in Korean subjects. Heterozygous mutant allele was found in four of 93 patients with PD, 0 of 32 patients with AD and one of 121 control subjects (59 stroke, 59 normal controls and four other psychiatric disorders), but no homozygous mutant allele was found. There were no statistically significant differences between the AD group and controls, and between the PD group and controls. In conclusion, we suggest that CYP2D6*4 polymorphism does not confer susceptibility to PD in the Korean population. Also, due to such a rare occurrence of the CYP2D6*4 polymorphism, we can not confirm the protective role of the polymorphism against AD in the Korean population.