脑啡肽酶基因多态性与阿尔茨海默病及血管性痴呆的相关性研究

目的 探讨陕西延安地区汉族人群中脑啡肽酶(NEP)基因多态性与阿尔兹海默(AD)和血管性痴呆(VD)的相关性。方法 选择2013年1月-2016年6月在本科治疗的138例AD患者作为AD组,57例VD患者作为VD组,同时随机选择同期在本院体检的老年体检健康者150例作为对照组,采用聚合酶链反应-限制性内切酶分析(PCR-RFLP)结合DNA直接测序法检测NEP基因rs989692位点和rs6776185位点基因型。结果 各组NEP基因rs989692位点基因型和等位基因分布频率无明显差异(P均>0.05)。对于rs6776185位点AD组和VD组与对照组比较,AA基因型和A等位基因分布频率均明显增多(P均<0.05)。AD组与VD组基因型和等位基因分布频率无明显差异(P均>0.05)。结论 NEP基因rs6776185位点A等位基因和AA基因型可能是陕西延安地区汉族人AD和VD发病的危险因素。     

尿激酶型纤溶酶原激活剂和脑啡肽酶基因多态性与阿尔茨海默病的相关性研究

目的探讨尿激酶型纤溶酶原激活剂（PLAU）和脑啡肽酶（NEP）基因单核苷酸多态性与散发性阿尔茨海默病（SAD）的相关性。方法提取138例SAD患者和125例正常志愿者的静脉血基因组DNA，应用多聚酶链式反应扩增目的基因片段，应用聚合酶链式反应一限制性片段长度多态性的方法进行基因分型。结果比较PLAU基因rs2227564位点的三种基因型分别与NEP基因rs3736187位点的三种基因型组合起来组成八种基因型频率在SAD组与对照组中的分布，结果显示有显著性差异（x^2=16．953，P=0．018）。SAD组TTCT基因型频率降低，TTCT缺失基因型频率增高，与对照组比较有显著性差异（x^2=6．464，P=0．011）。结论PLAU和NEP复合基因的多态性与SAD的发病具有相关性，TTCT基因型可能是SAD的保护基因型。     

胆固醇酯转运蛋白基因多态性与阿尔茨海默病的关系

目的 探讨胆固醇酯转运蛋白（CETP）基因Taq1B、I405V和D442G3个单核苷酸多态性在散发阿尔茨海默病（sporadic Alzheimer disease，SAD）发病机制中的作用。方法 应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法检测了107例SAD患者和115名性别和年龄匹配的健康老年人CETP基因和载脂蛋白E（ApoE）基因多态性分布特征。结果 对照组的D442G杂合子频率显著高于SAD组（分别为9％和2％，OR=0．202，95％CI，0．043—0．958，P=0．044）；ApoE基因分层后，ApoEε4携带者的D442G杂合子在对照组的频率显著高于SAD组（分别为22％和0，P=0．042），但ApoEε4非携带者的D442G杂合子频率在两组间差异无统计学意义（分别为6％和2％，P=0．284）。结论 D442G突变可能是AD的独立保护性因素，这种保护性作用在ApoEε4携带者明显。     

ApoE基因多态性与阿尔茨海默病的相关性研究

目的 探讨阿尔茨海默病（Alzheimer disease,AD）与载脂蛋白E（ApoE）基因多态性的关系.方法 采用PCR-RFL P方法,对68例晚发型AD（LOAD）、54例早发型AD（EOAD）和168例对照组进行ApoE基因型测定,对AD患者的ApoE基因多态性进行相关分析.结果 两组人群ε3/ε3基因型比例最大,未发现ε2/ε2基因型.APOEε4携带者的频率在LOAD组中是52.5%（43/80）,对照组16.1%（27/168）,其差别有显著性（χ^2=36.2,P＜0.000 1,RR=5.76,95%CI=3.17-10.47）;APOEε4携带者的频率与EOAD呈显著性相关（X^2=6.11,P=0.013 5,RR=2.40,95%CI=1.18-4.86）.结论 ε4等位基因与LOAD、EOAD呈显著性相关,是AD的危险因素之一.     

载脂蛋白D基因多态与散发性阿尔茨海默病的相关性

目的 通过检测载脂蛋白D基因(apolipoprotein D gene,ApoD)单核苷酸多态位点,探讨其与北方汉族人群散发性阿尔茨海默病(sporadic Alzheimer's disease,SAD)的相关性.方法 应用聚合酶链反应(PCR)及直接测序筛查ApoD基因所有外显子及其两端内含子多态位点.选取等位基因频率大于10%的位点,利用PCR-限制性片段长度多态性(PCR-RFLP)技术,采用病例-对照相关性研究方法 ,研究256例SAD患者以及294名健康人的ApoD多态位点与SAD发病的关系.同时对位点间的连锁不平衡及构建的单体型进行相关性分析.结果 ApoD第2号外显子存在T/C多态性(rs5952),第3号内含子(rs1568566)存在C/T多态性.ApoD rs5952 T/C和rs1568566 C/T等位基因频率和基因型频率在SAD组和对照组间的分布差异有统计学意义.Logistic回归分析表明携带rs5952C或rs1568566T等位基因分别增加SAD发病风险:校正后rs5952 χ2=9.282(P=0.002);rs1568566 χ2=5.072(P=0.024).进一步分析证实性别和ApoD多态性存在交互作用.rs5952-rs1568566位点间存在连锁不平衡.结论 北方汉族人ApoD基因存在第2号外显子rs5952和第3号内含子rs1568566 2个多态位点;ApoD多态可增加SAD发病风险;携带rs5952T或rs1568566C单体型可能对SAD的发病有一定的保护作用.     

Neprilysin基因单核苷酸多态性与阿尔茨海默病的相关性研究

目的探讨neprilysin基因单核苷酸多态性与中国北方汉族散发性阿尔茨海默病(sporadic Alzheimer's disease,SAD)的相关性。方法应用聚合酶链式反应-限制性片段长度多态性方法对157例SAD患者(AD组)和125例正常对照(对照组)进行neprilysin基因rs3736187位点单核苷酸多态性基因分型后,进行病例-对照相关分析。结果基因型的频率在病例组和对照组中分布差别有统计学意义(P<0.05),其中CC基因型与TT基因型相比,AD组CC基因型频率增高,TT基因型频率降低,CC基因型可以增加散发性AD的发病风险(P<0.05)。等位基因频率在两组中的分布差别无统计学意义(P>0.05)。结论Neprilysin基因rs3736187位点的CC基因型可能通过某种途径增加中国北方汉族散发性阿尔茨海默病的发病。     

载脂蛋白E基因多态性与早发性阿尔茨海默病的相关性

目的：探讨载脂蛋白E（ApoE）基因多态性与早发性阿尔茨海默病（EOAD）的相关性。方法：用扩增抗拒突变系统法检测103例EOAD患者、159例迟发性阿尔茨海默病（LOAD）患者和118例认知功能正常对照（Nc）者的ApoE基因多态性,分析其与EOAD患病的相关性。结果：EOAD组ApoE等位基因和基因型分布频率与正常对照组差异有显著统计学意义,与LOAD组差异无统计学意义;Logisfc回归证实携带ApoEg4与EOAD有显著相关性;ε4等位基因拷贝数的增加,可显著提高EOAD的患病率,但不影响EOAD的发病年龄。结论：ApoEg4是EOAD的独立危险因素,可显著增加EOAD的患病率。     

新疆维吾尔族和汉族阿尔茨海默病患者载脂蛋白E基因的多态性研究

目的 探讨新疆维吾尔族(以下简称维族)与汉族阿尔茨海默病(AD)患者载脂蛋白E(apoE)基因型及等位基因频率的分布及其异同.方法 在流行病学调查基础上,采用美国神经病学会、语言障碍和卒中-老年性痴呆和相关疾病学会制定的标准,诊断为很可能AD的患者209例(汉族98例、维族111例)及正常对照220名(汉族103名、维族117名),应用聚合酶链反应-限制性片段长度多态分析方法,检测两组apoE基因多态性.结果 (1)AD组及对照组组内维、汉两民族受试者apoE基因型频率和等位基因频率整体分布的差异无统计学意义(P＞0.05);但AD组ε3/4基因型(28.2%)和84等位基因频率(14.8%)均高于对照组(分别为13.2%和8.0%,P＜0.05).(2)在维、汉两民族中,AD组ε3/4基因型频率(维族:30.6%;汉族:25.5%)和ε4等位基因频率(维族:15.8%;汉族:13.8%)均高于本民族对照组(ε3/4基因型频率分别为维族:14.5%,汉族:11.7%;ε4等位基因频率分别为维族:9.4%,汉族:6.3%;P均＜0.05).(3)AD组男性维族患者ε3/4基因型频率(31%)高于对照组男性维族受试者(11%);AD组女性维族患者(16%)和汉族患者ε4等位基因频率(14%),分别高于对照组女性维族受试者(8%)和汉族受试者(7%;P均＜0.05).结论 apoE基因型及等位基因频率在维、汉民族间的分布相似;apoEe4等位基因是AD的危险因素,在维、汉两民族女性AD的发病中起重要作用.     

Pin1基因单核苷酸多态性与散发性阿尔茨海默病的相关性研究

目的 探讨中国汉族人群中Pin1基因单核苷酸多态性与散发性阿尔茨海默病(sporadic Alzheimer disease,SAD)的关系.方法 采用聚合酶链反应.限制性片段长度多态性(PCR-RFLP)技术,检测107例散发性阿尔茨海默病患者及110名正常对照的Pinl基因-667和-842位点基因多态性.结果 -667位点和-842位点SAD组和对照组基因型频率及等位基因频率差异均无统计学意义(P=0.098,P=0.102;P=0.835,P=0.594).将-667位点的3种基因型分别与-842位点的2种基因型组合起来也未发现差异有统计学意义(P=0.523).结论 未发现中国汉族人群中Pin1基N-667和-842位点多态性与SAD有相关性.     

载脂蛋白E基因多态性与阿尔茨海默病和帕金森病痴呆的相关研究

载脂蛋白Ｅ(ＡｐｏＥ)等位基因 4型 (ε4)被认为是导致Ａｌｚｈｅｉｍｅｒ病 (ＡＤ)发生的易患和危险基因之一。帕金森病(ＰＤ)和ＡＤ同属老年中枢神经变性疾病。而且帕金森病痴呆 (ＰＤＤ)与ＡＤ有许多相似之处。那么ＰＤＤ与ＡｐｏＥ基因多态性关系如何 ?为此 ,对ＡＤ、ＰＤ、ＰＤＤ和对照组的ＡｐｏＥ基因频率和基因型进行了对照研究 ,现将结果报道如下。资料和方法 :　入选病人主要来自北京市及华北地区的汉族居民。根据痴呆及原发性帕金森病的诊断标准 ,本组入选ＡＤ组 48例 ,其中男 34例 ,女 17例 ,平均年龄 (72 .6± 7.8)岁 ;ＰＤ组 …     

DISC1基因多态性与中国上海汉族人群阿尔茨海默病的关联研究

目的：探讨精神分裂症断裂基因(DISC1)rs821633,rs1000731单核苷酸多态性(SNP)与阿尔茨海默病(AD)的关系.方法提取中国上海汉族441例 AD 患者和749名健康对照组的 DNA,采用 Taqman 探针 SNP 基因分型技术测定 DISC1基因 SNP rs821633和 rs1000731位点的等位基因及基因型,检测两组受试者等位基因及基因型的频率分布差异.结果两组受试者中 rs821633不符合Hardy－Weinberg 平衡定律给予舍弃,rs1000731符合 Hardy－ Weinberg 平衡定律纳入,rs1000731位点的等位基因及基因型在两组受试者中分布比较,差异无统计学意义(P ＞0．05).结论 DISC1基因SNP rs1000731与 AD 无明显关联.     

Lack of association between the BDNF gene Val66Met polymorphism and Alzheimer disease in a Chinese Han population

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive neuronal loss in specific regions of the brain. Among the areas most severely affected are the basal forebrain cholinergic neurons and their projection regions, the hippocampus and the cortex. Several lines of evidence have made brain-derived neurotrophic factor (BDNF) an important candidate gene conferring risk for AD. Recently, several reports investigated the association between a single nucleotide polymorphism (Val66Met, rs6265) of the BDNF gene and AD but yielded ambiguous results. To figure out the association of this single nucleotide polymorphism in the BDNF gene with sporadic AD in a Chinese Han population, we analyzed 513 patients with AD and 575 controls for the genetic association studies. Our results indicated that the distribution of the BDNF genotypes and alleles did not differ significantly. Similar results were observed when the AD and control groups were stratified by age/age at onset and sex. Our data also showed that in the Chinese Han population, the frequencies of the BDNF Met allele (46.5%) and Val allele (53.5%) were significantly different from ethnic groups from Italy, Japan and the USA. The present data revealed no significant effect of the genotypes on the age at onset for developing AD, and no significant association between the genotypes and the severity of the disease.     

The Fas gene A-670G polymorphism is not associated with sporadic Alzheimer disease in a Chinese Han population

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by excessive neuronal loss, intracellular neurofibrillary tangles and extracellular deposition of amyloid beta-peptide (Abeta). The Fas antigen is a cell surface receptor-mediating cell apoptosis. Several lines of evidence have made Fas/Fas ligand induced apoptosis play an important role in the pathogenesis of AD. Moreover, the Fas gene is located on chromosome 10q24.1, a region of linkage to late-onset AD. Several reports have investigated the association between a single nucleotide polymorphism (SNP) that is located at position -670 of Fas gene and AD, but yielded ambiguous results. To figure out the association of this SNP with sporadic AD in Chinese Han population, we have analyzed 509 patients with AD and 561 controls for the genetic association studies. Our results indicate that the distribution of the Fas genotypes (chi(2) = 0.66, P = 0.72) and alleles (chi(2) = 0.70, P = 0.40) did not differ significantly. The similar results were observed when AD and control groups were stratified by age/age at onset and sex (P > 0.10). The present data revealed no significant effect of the genotypes on the age of onset for developing AD, and no significant association between the genotypes and the severity of the disease.     

NEDD9 gene polymorphism influences the risk of Alzheimer disease and cognitive function in Chinese older persons

Neural precursor cell expressed, developmentally down-regulated (NEDD9) gene was a new candidate risk gene for Alzheimer disease (AD). The CC genotype of a single nucleotide polymorphism rs760678 within this gene was associated with increasing risk of AD in a large study with white population. Our study aimed to replicate the initial report in Chinese population and explore its effect on cognitive performance. A total of 262 patients with AD, 293 patients with mild cognitive impairment, and 434 cognitive intact controls were recruited in the study. The result showed that G allele had a greater risk of AD (χ for trend test=5.61, df 1, P=0.018). The effects were mainly observed among Apolipoprotein E (APOE) ε4 noncarriers (χ for trend test=4.30, df 1, P=0.038). After adjustment of sex, age, education year, and APOE ε4 status by logistic regression, significant association between NEDD9 GG genotype and AD remained [OR=2.04, 95% confidence interval (CI)=1.02-4.08, P=0.044]. The scores of Cantonese version of the Mini-mental State Examination and Alzheimer's Disease Assessment Subscale-Cognitive subscale were associated with N polymorphism after adjusting for sex, age, education year, and ApoE ε4 status (Linear regression model, P<0.05). Our study identified rs760678 within NEDD9 gene in association with the risk of AD and cognitive performance in Chinese older persons. The fact that different alleles accounted for the risk in different population might suggest that there were ethnic group specific haplotypes that were primarily responsible for the predisposition.     

Association of CHUK gene polymorphism and ischemic stroke in the Han Chinese population

BackgroundRecently, the pivotal role of component of inhibitor of nuclear factor kappa B kinase complex (CHUK) in lipid levels and blood pressure has been reported, and hypertension and hyperlipidemia are common risk factors of ischemic stroke (IS). However, the association between CHUK and IS has not yet been explored. This study aims at evaluating the relationship of CHUK polymorphisms (rs3808916, rs2230804 and rs3808917) and IS risk as well as IS-related risk factors. Methods: CHUK mRNA expression was detected between 53 IS patients and 53 healthy controls using quantitative real-time polymerase chain reaction (qRT-PCR). A total of 816 IS patients and 816 age- and sex-matched healthy controls were genotyped using the Sequenom MassARRAY iPLEX platform. Results: CHUK mRNA was highly expressed in IS patients compared with healthy subjects (P＜0.001). No significant associations were observed between rs3808916, rs2230804, rs3808917 and IS susceptibility (P＞0.05). Moreover, haplotype analysis showed that no haplotype of CHUK polymorphisms was associated with IS (P > 0.05). However, rs2230804 was related to diastolic blood pressure (DBP) of IS patients (P = 0.035), while rs3808917 was associated with triglyceride (TG) levels (P = 0.046). Conclusions: The CHUK expression is involved in the development of IS. CHUK variants rs2230804, and rs3808917 may affect blood pressure and lipid levels of IS patients. However, CHUK rs3808916, rs2230804 and rs3808917 polymorphisms are not associated with IS risk.     

5，10-亚甲基四氢叶酸还原酶基因多态性对中国汉族人群缺血性脑血管病可能不是一个危险因素：一个临床荟萃分析

[摘要] 目的：估评5,10 -甲基四氢叶酸还原酶（MTHFR）基因多态性（TT基因型 或T等位基因）是否是缺血性脑血管疾病（ICVD）的危险因素。方法：通过电脑查找Medline数据库上所有公开发表的有关缺血性脑血管病MTHFR的基因型研究、这些研究均是针对人类的病例对照研究。有18个研究小组的论文资料被鉴定适合作荟萃分析。在这18个研究小组中有6个是专门针对中国汉族人群进行的研究,被特别提取出来进行分析。结果：4295例缺血性脑血管病例和6169例正常对照在这一研究报告中使用了荟萃分析。脑血管病组和正常对照组比较,不仅MTHFR基因的TT基因型两组有显著性差异（X2 =15.74, P﹤0.01)、而且T等位基因频率两组有显著性差异（X2 =9.19, P﹤0.01)。另外,就中国汉族人群中脑血管病组和正常对照组比较,MTHFR基因的TT基因型(X 2 = 1.076, P﹥0.05)和T等位基因频率( X 2 = 2.434, P﹥0.05 )两组分别比较均无显著性差异。 结论：该荟萃分析表明,MTHFR基因的TT基因型和T等位基因在世界较大范围内是缺血性脑血管病的危险因素;但是针对中国汉族人群而言,MTHFR基因的TT基因型和T等位基因均不是缺血性脑血管病的危险因素。     

ARHGEF10 gene polymorphism is closely associated with the risk of ischemic stroke in Northern Han Chinese population

Stroke is a common disease with high mortality and morbidity. It is of high importance to identify biomarkers of stroke. Rho guanine nucleotide-exchange factor(GEF) 10 (ARHGEF10) gene polymorphism has been found to be associated with various human diseases, but its correlation with stroke remains unknown. This study aims to evaluate the potential association of the single nucleotide polymorphisms (SNPs) of ARHGEF10 with ischemic stroke (IS) in northern Han Chinese population. Three SNPs of ARHGEF10 gene were analyzed in 385 IS patients and 362 hypertension control patients using the ligase detection reaction (LDR) method. Logistic regression analysis demonstrated that GG genotypes of SNP rs2280887 were associated with an increased risk of IS in dominant, recessive, and additive models. Moreover, SNP rs9657362 and SNP rs4480162 were significantly associated with IS in dominant and additive models. These results indicate that ARHGEF10 gene polymorphisms may affect IS risk in northern Han Chinese.     

Association between cathepsin D polymorphism and Alzheimer's disease in a Chinese Han population

Cathepsin D (CTSD) is an intracellular aspartyl protease, which is active in the endosomal/lysosomal system. CTSD may play a role in Alzheimer's disease (AD) through cleaving the amyloid precursor protein into beta-amyloid peptide and degrading tau protein into fragments. A functional polymorphism in exon 2 of the cathepsin D gene (C-->T, Ala224Val) has recently been reported to increase the risk for AD in some of the Caucasian populations, with a significant overrepresentation of the T allele, but these reports have not been universally duplicated. We performed an association study between CTSD polymorphism and AD in 156 sporadic AD patients and 183 controls of Chinese Han ethnicity. Our data revealed that the distribution of CTSD genotypes and alleles was similar in patients and controls. No direct association was found between CTSD polymorphism and AD risk. There might be a weak synergistic interaction between CTSD T and APOEepsilon4 allele in increasing the risk for developing AD.