雌激素受体α基因多态性与卒中后抑郁的相关性

目的 探讨雌激素受体(ER)α基因多态性与卒中后抑郁( PSD)的相关性.方法 应用PCR技术对45例PSD患者及49例脑卒中后非PSD患者ERα Pvu Ⅱ及Xba Ⅰ基因型和等位基因频率进行比较.结果 两组以ERα基因ppxx基因型及p、x等位基因出现的频率最高;两组间基因型和等位基因频率差异无统计学意义.结论 ERα基因Pvu Ⅱ和Xba Ⅰ基因多态性与PSD发病无关.     

精神分裂症核心家系与脑源性神经营养因子基因C270T多态性研究

目的 研究脑源性神经营养因子(brain-derived neurotrophic factor,BNDF)基因C270T多态性与精神分裂症的关系.方法 在91个精神分裂症核心家系中,以聚合酶链反应和限制性片段长度多态性的方法对BDNF基因C270T多态性进行检测.采用单体型相对风险(haplotype relative risk,HRR)和传递不平衡检验(transmission/disequilibrium test,TDT)对精神分裂症与BDNF基因C270T多态性位点进行关联分析,以及分析该位点与阳性和阴性症状量表(positive and negative syndrome scale,PANSS)各因子分的关系.结果 HRR分析显示,BDNF基因C270T多态性与精神分裂症无关联(?掊 2 ＝ 3.39,P ＞ 0.05).TDT分析未发现BDNF基因C270T多态性位点在精神分裂症患者中存在传递不平衡(?掊 2 ＝ 3.2,P ＞ 0.05).携带T等位基因(CT和TT基因型)的患者阳性症状分高于未携带T等位基因(CC基因型)的患者(t ＝ -2.11,P ＝ 0.04).结论 本研究未发现BDNF基因C270T多态性和精神分裂症关联,但发现T等位基因可能与阳性症状存在关联.     

雌激素受体基因多态性与多发性硬化

目的探讨雌激素受体(ER)基因多态性与云南多发性硬化(MS)女性病人的相关性。方法应用限制性片段长度多态性聚合酶链反应(RFLP-PCR)分析方法,检测24例MS女性患者和30例性别、年龄相匹配的健康对照者ER基因PvuⅡ和XbaⅠ酶切多态性。结果 MS组P等位基因频率与对照组相比差异有显著性(X2=4.296,P<0.05);X等位基因在两组间比较无显著性(X2=0.665,P>0.05);联合基因分析,两组间其基因型频率分布差异无显著性(X2=6.073,P>0.05)。结论 ER基因PvuⅡ酶切多态性与MS具有相关性,可能是云南汉族女性发病的危险因素之一;XbaⅠ酶切多态性与MS无相关性。     

散发性Alzheimer病患者脑源性神经营养因子基因C270T多态性的研究

目的探讨中国汉族人群散发性Alzheimer病(SAD)患者脑源性神经营养因子(BDNF)基因C270T多态性与AD发病的关系。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55例SAD患者和80名年龄、性别匹配的健康人(正常对照组)BDNF基因C270T多态性,比较两组基因型分布和等位基因频率。结果正常对照组BDNFC270T基因型及等位基因频率分布符合Hardy-Weinberg定律(χ2=0.167,P=0.682),SAD组基因型[C/C型52例(94.5%),C/T型3例(5.5%)]及等位基因频率(C97.27%,T2.73%)分布与正常对照组[C/C型74例(92.5%),C/T型6例(7.5%);C96.25%,T3.75%]比较差异无统计学意义。结论中国汉族人群BDNF基因C270T多态性与SAD的发病无明显关系。     

雌激素受体基因多态性与多发性硬化

目的　探讨雌激素受体 ( ER)基因多态性与多发性硬化 ( MS)的相关性。方法　应用限制性片段长度多态性聚合酶链反应 ( RFLP-PCR)分析方法 ,检测 63例 MS患者和 95例对照者 ER基因 Pvu 和 Xba 酶切多态性。结果　MS组 P等位基因频率明显高于对照组 ( P=0 .0 2 2 ,OR=1 .70 8,95 % CI:1 .0 78～ 2 .70 5 ) ,且在女性 MS患者 P等位基因分布频率和对照组间差异有显著性 ( P =0 .0 48,OR =1 .82 4,95 % CI :1 .0 0 3～ 3 .3 1 8)。MS组 Ppxx基因型频率明显高于对照组 ( P =0 .0 0 6)。结论　ER基因 Pvu 酶切多态性与 MS存在相关性 ,可能是 MS发病的危险因素之一 ,尤其是携带 P等位基因的女性更易患 MS;Xba 酶切多态性与 MS无相关性     

儿童精神分裂症患者脑源性神经营养因子基因C270T多态性与脑室扩大及微小躯体异常的关系

目的 调查儿童精神分裂症患者脑源性神经营养因子基因(BDNF)C270T多态性与脑室扩大及微小躯体异常(MPA)的关系.方法 采用横断面研究的方法 ,用聚合酶链反应-限制性片段长度多态性方法 ,分析204例儿童精神分裂症患者和210名健康对照的BDNF基因C270T多态性;用CT测量患者的脑室值,采用Waldrop编制的躯体异常量表(WS)修改版评定MPA发生情况.结果 ①患者组BDNF基因C270T多态性的C/T和T/T基因型频率及T等位基因频率均高于对照组(X2=24.56,P＜0.01;X2=24.04,P＜0.01);②不同基因型患者组之间各脑室值比较差异均无统计学意义(P＞0.05);T/T与C/T基因型患者合并后哈氏值高于C/C型患者(t=2.28,P＜0.05);③T/T和C/T型合并后与C/C型患者比较,两组患者手部WS评分及WS总分的差异均具有统计学意义(Z=2.34.P＜0.05;t=2.10;P＜0.05);④WS总分与哈氏值及三脑室宽度存在正相关(r=0.26,P＜0.01;r=0.29;P＜0.01),与前角指数存在负相关(r=-0.18,P＜0.05).结论 儿童精神分裂症患者BDNF基因C270T多态性与微小躯体异常有关,并可能与脑室扩大也有关.     

脑源性神经营养因子基因C270T多态性与儿童精神分裂症的关系

目的 探讨脑源性神经营养因子(BDNF)基因C270T多态性与儿童精神分裂症的关系.方法 采用病例对照研究,用聚合酶链反应-限制性片段长度多态性方法,分析204例儿童精神分裂症患者和210名健康对照的BDNF基因C270T多态性;进行阳性与阴性症状量表(PANSS)评定,用Andremson阳性与阴性精神分裂症分型标准将患者分为阴性症状为主型(阴性组)和阳性症状为主型(阳性组).结果 ①患者组和对照组间BDNF基因C270T多态性的基因型频率差异有统计学意义(χ2=24.56,P<0.01),前者的C/T型和T/T型频率高于后者;患者组等位基因T频率显著高于对照组(χ2=24.04,P<0.01);②阴性组、阳性组、对照组3组间基因型及等位基因分布的差异均有统计学义(χ2=37.93,P<0.01;χ2=38.90,P<0.01);两两比较显示,阴性组、阳组分别与对照组比较,基因型及等位基因分布差异均有统计学义(P<0.001).③不同基因型患者组之间PANSS各因子分和总分差异均无统计学意义(P>0.05).结论 BDNF C270T多态性与儿童精神分裂症有关,但与具体临床表现之间无明显的关系.     

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.     

白细胞介素-1B多态性与神经胶质瘤的关联

目的 探讨白细胞介素-1B(IL-1B)多态性与神经胶质瘤的相关性.方法 采用聚合酶链反应-限制性片段长度多态性检测152例神经胶质瘤患者和201例正常对照组IL-1B-511C/T和-31T/C多态性.结果 IL-1 B-511 C/T位点:与CC基因型相比,TT基因型显著增加了神经胶质瘤的发病风险(x2 =5.61,P=0.021).与C等位基因相比,T等位基因显著增加了神经胶质瘤的发病风险(x2 =5.71,P=0.019).未发现IL-1B-31T/C多态性频率分布在对照组和神经胶质瘤组之间存在明显差异.IL-1B-511C/T和-31T/C两位点单倍型分析显示,-511C/-31T单倍型显著降低了神经胶质瘤的发病风险(x2=4.89,P=0.03),-511T/-31C单倍型显著增加了神经胶质瘤的发病风险(x2=18.55,P＜0.001).结论 IL-1B可能是中国人群神经胶质瘤发病的易感基因.     

上海地区汉族人群LMTK2与MSMB基因多态性与前列腺癌的易感性

目的：探讨中国上海地区汉族人群中LMTK2与MSMB基因多态性与前列腺癌遗传易感性的关系。 方法：采用病例对照研究,提取200例前列腺癌患者(病例组)和200例非前列腺癌健康人(对照组)外周血中基因组DNA,应用ABI 3730 XL测序仪分析病例组和对照组的LMTK2基因rs6465657位点以及MSMB基因rs10993994位点的多态性,比较不同基因型与前列腺癌易感性的关系。 结果：MSMB基因rs10993994位点密码子T/C基因型的个体其前列腺癌发病风险是C/C基因型的1.62倍(OR =1.62, 95% 可信区间：1.12~2.27),携带MSMB基因rs10993994位点等位基因T(T/T,T/C)的个体发生前列腺癌的风险性是C/C基因型的0.96倍(OR =0.96, 95% 可信区间：0.82~1.11)。LMTK2基因rs6465657位点密码子C/C基因型的个体其前列腺癌发病风险与T/C基因型无明显差异。 结论：中国上海地区汉族人群中MSMB基因rs10993994位点多态性可能对前列腺癌遗传易感性有影响,而LMTK2基因rs6465657位点对前列腺癌遗传易感性无明显影响。     

Prophylactic lithium response and polymorphism of the brain-derived neurotrophic factor gene

INTRODUCTION: Brain-derived neurotrophic factor (BDNF) has been involved in the pathogenesis of bipolar mood disorder and in the mechanism of mood-normalizing action of lithium. The aim of this study was to find a possible association between lithium prophylactic effect in bipolar patients and two polymorphisms of BDNF gene. METHODS: Eighty-eight patients (35 males, 53 females) with bipolar illness were studied. Duration of lithium prophylaxis ranged between 5-27 years (mean 15 years). Three categories of prophylactic lithium response were delineated: excellent responders (ER), partial responders (PR) and non-responders (NR). All patients were genotyped for two polymorphisms of BDNF gene: Val66Met and -270C/T. RESULTS: The Val/Met genotype of Val66Met polymorphism occurred more frequently (p = 0.037) and there was a trend for a higher incidence of Met allele (p = 0.076), in ER than in NR. A trend for C/T genotype and T allele of -270C/T polymorphism was observed to occur more frequently in ER than in NR (p = 0.057 and p = 0.065, respectively). CONCLUSION: The data obtained suggest that polymorphism of BDNF gene may be connected with a quality of lithium prophylaxis.     

A novel polymorphism of the brain-derived neurotrophic factor (BDNF) gene associated with late-onset Alzheimer's disease

Several lines of evidence have suggested altered functions of the brain-derived neurotrophic factor (BDNF) in the pathogenesis of neurodegenerative diseases including Alzheimer's disease (AD). In the search for polymorphisms in the 5'-flanking and 5'-noncoding regions of the BDNF gene, we found a novel nucleotide substitution (C270T) in the noncoding region. We performed an association study between this polymorphism and AD in a Japanese sample of 170 patients with sporadic AD (51 early-onset and 119 late-onset) and 498 controls. The frequency of individuals who carried the mutated type (T270) was significantly more common in patients with late-onset AD than in controls (P = 0.00004, odds ratio: 3.8, 95% CI 1.9-7.4). However, there was no significant difference in the genotype distribution between the patients with early-onset AD and the controls, although this might be due to the small sample size of the early-onset group. Our results suggest that the C270T polymorphism of the BDNF gene or other unknown polymorphisms, which are in linkage disequilibrium, give susceptibility to late-onset AD. We obtained no evidence for the possible interactions between the BDNF and apolipoprotein E (APOE) genes, suggesting that the possible effect of the BDNF gene on the development of late-onset AD might be independent of the APOE genotype.     

脑源性神经营养因子基因单体型与散发性Alzheimer病的关系

目的分析汉族人群中脑源性神经营养因子(BDNF)基因G196A、C270T、G11757C和G712A单核苷酸多态性(SNPs)和单体型频率与散发性Alzheimer病(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106例sAD患者和110名健康对照者BDNFG196A、C270T、G11757C和G712A基因型和等位基因频率,采用SHEsis软件进行连锁不平衡及单体型分析。结果sAD组及健康对照组C270T位点T等位基因频率分别为0.9%及4.5%,G712A位点GG基因型频率分别为95.4%、91.8%,A等位基因频率分别为0.5%及4.5%;两组比较差异有统计学意义(均P<0.05)。单体型分析显示,sAD组和健康对照组GTGA频率分别为0.5%和3.2%,差异有统计学意义(P<0.05)。结论BDNF基因多态性可能与中国汉族人群sAD发病有关。     

C677T polymorphism of methylenetetrahydrofolate reductase gene affects plasma homocysteine level and is a genetic factor of late-onset Alzheimer's disease

Background: Elevated plasma homocysteine levels are known as a risk for atherosclerotic vascular disease and venous thrombosis and have been shown as a risk for late‐onset Alzheimer's disease (LOAD). Method: To examine the effect of genetic factors predisposing to elevated plasma homocysteine levels on the occurrence of LOAD, we determined the genotype of a C677T polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and a variable number tandem repeat (VNTR) spanning exon 13–intron 13 boundary of cystathionine β‐synthase (CBS) gene in patients with LOAD and community‐based control subjects. Results: Logistic regression indicated that the MTHFR‐T allele was a risk for LOAD (P < 0.05), independently from apolipoprotein E‐?4 (APOE‐?4) allele. Kaplan–Meier tests showed that in APOE‐?4 non‐carriers, individuals with the MTHFR‐TT genotype have occurences of LOAD earlier than those with the MTHFR‐CC genotype (P < 0.05). Multiple regression analysis indicates that MTHFR‐T allele increases plasma homocysteine levels (P = 0.0002), while the number of X chromosomes decreases (P = 0.01). Plasma homocysteine level was not correlated with age, plasma albumin reflecting nutritional condition, and the dose of APOE‐?4 allele. The CBS‐20 VNTR allele showed the same trend to increase plasma homocysteine level as the MTHFR‐T allele, but a risk effect for LOAD was not evident. Conclusion: A genetic propensity for elevated plasma homocysteine levels, explained by the MTHFR‐T allele encoding defective enzymatic function, is involved in the development of LOAD, particularly in APOE‐?4 non‐carriers, and that homocysteine metabolism could be a preventive target to LOAD in the elderly.     

Association of MTHFR gene polymorphism C677T with susceptibility to late-onset alzheimer’s disease

Increased total plasma homocysteine (t-Hcy) levels are found to be associated with Alzheimer's disease (AD). Because the methylenetetrahydrofolate reductase (MTHFR) gene encodes a key enzyme that influences the metabolism of homocysteine, it has been considered as a possible genetic risk factor for AD. Although the MTHFR gene C677T polymorphism has a significant impact on reducing enzyme activity and increasing t-Hcy concentrations, the association between the C677T polymorphism and AD remains inconclusive. To determine whether the MTHFR gene C677T polymorphism contributes to the risk for late-onset AD (LOAD) in Chinese, we have investigated 104 sporadic LOAD patients and 130 healthy controls. The strong associations of the TT genotype and T-allele with LOAD (p 0.001, OR 5.73 95% CI 1.85-17.72, and p 0.002, OR 1.89 95% CI 1.25-2.86) were found. After stratifying by apolipoprotein E allele 4 (APOE epsilon4) status, increased LOAD risks associated with the TT genotype only in the APOE epsilon4 noncarriers (chi2=8.92, df=1, p=0.003) and with the T-allele in either group (chi2=5.18, df=1, p=0.023 and chi2=5.53, df=1, p=0.019) were seen. These results suggest that as an APOE epsilon4 allele-dependent risk factor, the MTHFR gene C677T polymorphism is involved in developing LOAD in Chinese.     

TM4SF5基因与阿尔茨海默病的相关性研究

目的 探讨跨膜蛋白4超级家族5 (transmembrane 4 superfamily member 5,TM4SF5)基因多态性、载脂蛋白E(ApoE)基因多态性和阿尔茨海黙病(AD)的相关性.方法 通过使用TaqMan-PCR法检测单核苷酸多态性(SNP)方法,在376例日本人AD患者,包括323例迟发型AD(LOAD)、53例早发型AD(EOAD)和377例非痴呆对照组中观察TM4SF5基因rs4790230(-791T/C)、rs746988(+1528T/C)、rs2302328(+11228C/A)及APOE基因的多态性分布,并分析与AD的相关性.结果 (1) TM4SF5基因rs4790230(-791T/C)C/C纯合子频率在EOAD中明显高于对照组(0.70比0.52,P值为0.017) ;rs2302328(+ 11228C/A)携带A等位基因者频率在总AD中略高于对照组(0.88比0.84,P值为0.05);(2)进一步在非APOE4携带者中分析显示rs4790230(-791T/C)C/C纯合子频率在EOAD中仍明显高于对照组(0.85比0.53,P＜0.001);(3)单倍型分析显示病例组C-C-A型与C-T-A型频率分别高于对照组(0.29比0.21;0.35比0.16;P＜0.001);病例组C-T-C型频率低于对照组(0.12比0.28;P＜0.001).结论 TM4SF5基因rs4790230(-791T/C)多态位点独立于APOE与EOAD存在相关性,三位点单倍型C-C-A型与C-T-A型增加了AD的发病风险.     

The brain-derived neurotrophic factor gene as a possible susceptibility candidate for Alzheimer's disease in a chinese population

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophic factor family, may represent a candidate gene conferring susceptibility to Alzheimer's disease (AD). This is because it has an important role in neuronal survival, and a decreased central level of BDNF is observed in AD. Some previous studies, though not all, have demonstrated that BDNF C270T polymorphisms might be associated with AD susceptibility. We examined the association of the C270T polymorphisms with sporadic AD in a Chinese cohort of 175 AD patients and 189 controls. We also tested BDNF Val66Met-C270T haplotypes for an interaction with the apolipoprotein E upsilon4 (APOE4) allele in AD. The results showed that the frequency of the 66Val allele was significantly lower in AD than controls (p = 0.031), but no significant difference in C270T allele or genotype frequencies was observed between AD cases and controls. Global case-control haplotype analysis showed that there is significant difference in haplotype distribution between both groups (p = 0.033). Stratification of the data according to the APOE status showed that in APOE4 allele bearers there was no significant difference in the frequency of haplotype 66Val-270C between AD and controls (p = 0.125), although there was a significant difference between the two groups in non-APOE4 carriers (p = 0.002). These results suggest that BDNF genetic variation may possibly affect the risk for AD, particularly in subjects who are negative for APOE4.     

Association of estrogen receptor gene polymorphism in patients with degenerative lumbar spondylolisthesise

Objective

The purpose of this study was to investigate the possible association of estrogen receptor alpha (ERα) gene polymorphisms in a cohort of degenerative spondylolisthesis (DS) patients.

Methods

Accordingly, the authors examined the association between DS and ERα gene polymorphisms in 174 patients diagnosed with DS. The Pvu II and Xba I polymorphisms, bone mineral density at the lumbar spine and femoral neck, and biochemical markers were analyzed and compared in the 174 patients with DS and 214 patients with spinal stenosis (SS).

Results

A comparison of genotype frequencies in DS and SS patients revealed a significant difference for the Pvu II polymorphism only (p=0.0452). No significant difference was found between these two groups with respect to the Xba I polymorphism, BMD or biochemical markers. No significant association was found between the Pvu II polymorphism of ERα and BMD, vertebral slip or biochemical markers in patients with DS.

Conclusion

These results suggest that the ERα gene polymorphism using Pvu II restriction enzyme influences the prevalence of DS.