胰岛素受体底物-2的Gly1057Asp基因多态性与颈动脉粥样硬化性狭窄相关性的研究

目的 探讨胰岛素受体底物-2的Gly1057Asp基因多态性与颈动脉粥样硬化性狭窄的相关性。方法 选择96例行颈部血管彩超示颈动脉狭窄≥50%的北方汉族人为实验组以及同期79例体检健康者作为对照组,通过聚合酶链反应-限制性片段长度多态性分析(PCR-RFLP)技术检测所有入选患者的Gly1057Asp基因多态性,比较2组的等位基因频率、基因型频率以及Gly1057Asp基因多态性对颈动脉狭窄的影响。结果 实验组中G等位基因频率(78.6%)明显高于对照组(68.4%)(P<0.05); 实验组中G/A+A/A基因型频率(36.5%)明显低于对照组(51.9%)(P<0.05)。携带等位基因G的个体患有颈动脉粥样硬化性狭窄的风险是非等位基因G携带者的1.99倍(OR=1.994,95%CI=1.068～3.761)。结论 胰岛素受体底物-2的Gly1057Asp基因多态性可能与颈动脉粥样硬化性狭窄有关,等位基因G可能是颈动脉粥样硬化性狭窄的独立危险因素。     

基质金属蛋白酶-9基因多态性与缺血性脑卒中的相关性

目的探讨基质金属蛋白酶-9(matrix metalloproteinases-9,MMP-9)基因多态性与缺血性脑卒中的相关性。方法运用多重小测序技术(multiplex SNa Pshot)分析粤西地区251例缺血性脑卒中患者和96例健康对照组MMP-9基因(rs3787268、rs3918241、rs3918242)的多态性分布,并分析与缺血性脑卒中的相关性。结果 (1)与对照组相比,病例组rs3787268基因型频率有统计学差异(P=0.042),在隐性模型中A/A基因型的个体患病风险升高(OR=2.21,P=0.046);(2)rs3918242基因型频率亦有统计学差异(P=0.007),在显性模型中,携带T基因型的个体患病风险升高(OR=2.14,P=0.009);(3)其中rs3787268在大动脉粥样硬化(large artery atherosclerosis,LAA)亚型组的基因型分布与对照组相比有统计学差异(P=0.039),而非LAA亚型中无统计学差异;rs3918242在LAA亚型组的基因型和等位基因频率与对照组相比分别有统计学差异(P=0.009,P=0.047),在非LAA亚型中无统计学差异。结论 MMP-9基因rs3787268和rs3918242多态位点突变可能与中国粤西地区汉族人群缺血性脑卒中的发病风险相关;并主要可能增加了LAA型脑卒中的发病风险。     

Lack of association of the RTN4R genetic variations with risk of schizophrenia and SPEM abnormality in a Korean population

This study examined the association of the reticulon 4 receptor (RTN4R) gene with schizophrenia and smooth pursuit eye movement (SPEM) abnormality in a Korean population. Although we failed to provide convincing evidence that RTN4R is associated with schizophrenia development and SPEM impairment, our findings may be useful for further genetic studies.     

The association between BsmI polymorphism and risk factors for atherosclerosis in patients with epilepsy taking valproate

PurposeTo evaluate the association between the BsmI polymorphism and vascular risk factors or metabolic syndrome in patients with epilepsy treated with valproate.MethodsWe performed a cross-sectional study to determine glucose homeostasis, lipid profile, and evidence of metabolic syndrome, as well as the BsmI polymorphism in seizure free adults with epilepsy.ResultsWe recruited 75 patients with epilepsy to the current study. The frequency of the BsmI polymorphism was 22.7%. We found that patients with BsmI polymorphism had significantly higher total levels of triglycerides, total cholesterol, HDL-C and LDL-C. There were no differences in terms of fasting blood glucose level and fasting insulin levels between patients with the BsmI polymorphism and those with the wild type vitamin D receptor (VDR) gene. Insulin resistance was identified in 6 of 17 patients with the BsmI polymorphism, and 18 of 58 patients with the wild type VDR gene. We calculated the homeostasis model assessment (HOMA) index and found no difference in HOMA levels between the groups. Systolic blood pressure was higher in patients with the BsmI polymorphism. There was a higher prevalence of metabolic syndrome in patients with the BsmI polymorphism than in patients with the wild type gene. The prevalence of metabolic syndrome in BsmI polymorphism carriers was 64.7% compared with 41.4% in patients with the wild type VDR gene.ConclusionYoung patients with epilepsy taking valproate who carry the BsmI polymorphism are at an increased risk of having vascular risk factors.     

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.     

聚集素基因多态性与Alzheimer病相关性的Meta分析

目的探讨聚集素(CLU)基因rs11136000多态性与Alzheimer病(AD)的相关性。方法运用Meta分析的方法检索PubMed、EMBASE、AlzGene、CBM、CHKD等数据库,收集符合纳入标准的CLU基因多态性与AD关系相关病例-对照研究文献。对纳入文献进行H-W遗传平衡检验及异质性检验,选择固定效应模型,以CLU基因rs11136000位点(TT+TC)/CC基因型及T/C等位基因分布的优势比(OR)和95%可信区间(CI)为效应指标,利用RevMan 5.0、Stata 11.0软件计算合并OR值及95%CI;偏倚分析评估发表偏倚。结果纳入10篇文献共29个研究群体。按种族分为高加索亚组、亚洲亚组、非洲亚组、西班牙亚族及其他种族亚组,组内无显著异质性。AD高加索亚组与对照组比较,CLU基因rs11136000(TT+TC)/CC基因型和T/C等位基因分布的合并OR=0.83(95%CI:0.79～0.86)和0.88(95%CI:0.85～0.90),总体效应检验Z=8.44、9.74(均P<0.001)。亚洲亚组、非洲亚组、西班牙亚组及其他种族亚组(TT+TC)/CC基因型和(或)T/C等位基因分布差异无统计学意义。偏倚分析未发现明显发表偏倚。结论 CLU基因rs11136000多态性与高加索人群AD易感性相关,携带T等位基因可能降低AD发病风险。其对于亚洲人、非洲裔、西班牙人及其他种族人群的影响尚不确定。     

白芍总甙对局灶性脑缺血大鼠脑组织炎症信号表达的影响

目的观察白芍总甙对局灶性脑缺血(Focal Cerebral ischemic,FCI)大鼠脑组织Toll样受体4(TLR4)基因表达的作用。方法参照longa等方法制成大鼠局灶性大脑中动脉梗死(MCAO)模型,将80只SD雄性大鼠随机分为假手术组,溶剂组,白芍总甙低、高两个剂量组,采用RT-PCR法检测缺血灶周围脑组织TLR4基因表达水平。结果生理盐水组TLR4基因相对表达均明显高于假手术组(P<0.01);白芍总甙中高剂量组TLR4相对表达量明显低于生理盐水组(P<0.01)。结论生理盐水组大鼠缺血灶周围脑组织TLR4基因高表达,白芍总甙对TLR4表达有抑制作用,这可能是其抗炎作用的机理之一。     

Lack of association between synapsin II (SYN2) gene polymorphism and susceptibility epilepsy: a case-control study and meta-analysis

Objective: The SYN2 rs3773364 A>G polymorphism has been proposed to be involved in susceptibility to epilepsy, but research results have been inconclusive. The aim of this study was to investigate the association between the SYN2 rs3773364 A>G polymorphism and susceptibility against epilepsy in a case–control study and a meta‐analysis. Methods: The SYN2 rs3773364 A>G polymorphism was successfully genotyped in 1182 samples (618 epilepsy patients) of Chinese, Indian, and Malay ethnicities. Meta‐analysis of the related studies, including this case–control study, was performed under alternative genetic models. Results: Data from the case–control study indicated no allelic and genotypic association of this locus with susceptibility to epilepsy in the tri‐ethnic Malaysian population. Similar finding was obtained by stratified analysis by epilepsy syndrome for idiopathic epilepsy. These results were verified by meta‐analysis of the related pooled data. Conclusions: Our study indicated that SYN2 rs3773364 A>G polymorphism is not a risk factor for susceptibility to epilepsy. Synapse 2011. © 2011 Wiley‐Liss, Inc.     

染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的Meta分析

目的 缺血性卒中（ischaemic stroke,IS）是一种与遗传因素密切相关的多基因疾病。以单核苷酸多态性（single nucleotide polymorphism,SNP）为遗传标记系统的全基因组关联研究（Genomewide Association Studies,GWAS）发现染色体9p21多态性是血管粥样硬化的独立危险因素,与动脉粥样硬化性缺血性卒中易感风险相关;但由于样本量较小,通过比较等位基因频率分布,显示其在病例组与对照组之间无明显差异,这突出了更大规模研究的必要性。本研究拟对目前已发表的有关染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的病例-对照研究严格质量控制后进行Meta分析,旨在明确染色体9p21与动脉粥样硬化性缺血性卒中易感相关性的SNP种类,并对其与疾病发生风险的大小进行评估。方法 联合检索目前已发表的全部有关染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的病例-对照研究,制定严格的纳入排除质量控制标准,应用国际Cochrane系统评价协作网提供的Meta分析专用软件RevMan5.0对数据进行Meta分析,用森林图（Forest Plot）展示各个研究的OR（odds ratio）值及95％可信区间（confidence interval,CI）以及合并统计的OR值及95%CI,系统评价染色体9p21与动脉粥样硬化性缺血性卒中易感相关性的SNP在病例组与对照组分布有无差异,分析得到染色体9p21多态性与动脉粥样硬化性缺血性卒中易感相关性的统计学意义。结果 进入Meta分析的资料涉及6项跨越欧洲与北美洲的多中心临床病例-对照研究。进入Meta分析的基因多态性涉及染色体9p21上的7种SNP：rs7044859、rs496892、rs564398、rs7865618、rs1537378、rs2383207及rs10757278。其中,rs564398、rs7865618、rs1537378、rs2383207和rs10757278与动脉粥样硬化性缺血性卒中相关性具有统计学意义,与动脉粥样硬化性缺血性卒中易感风险相关。而rs7044859、rs496892与动脉粥样硬化性缺血性卒中相关性无统计学意义。结论 本研究发现染色体9p21的5种SNP（rs564398、rs7865618、rs1537378、rs2383207及rs10757278）与动脉粥样硬化性缺血性卒中具有易感相关性,染色体9p21变异被认为是血管粥样硬化的危险因素,是动脉粥样硬化性缺血性卒中的候选易感基因。     

microRNA133b的单核苷酸多态性与脑卒中的相关性的初步探讨

目的 探讨microRNA133b的SNP单核苷酸多态性(single nucleotide polymorphism, SNP)与脑卒中的相关性。方法 收集本院神经内科2012年9月～2016年9月1200例脑卒中患者的临床资料,将其定义为观察组,同时以1200例体检健康者作为正常对照组,观察2组血液中的microRNA133b的表达水平、microRNA133b的单核苷酸多态性以及各组中相关的临床参数。结果 观察组中脑卒中患者的饮酒史和高血压病史的比例都显著高于正常对照组(P<0.05); 观察组脑卒中患者血清总胆固醇(total cholesterol,TG)、低密度脂蛋白(Low density lipoprotein,LDLC)、空腹血糖、甘油三酯(triglyceride,TC)以及C反应蛋白的水平都显著高于正常对照组(P<0.05); 观察组脑卒中患者血清中高密度脂蛋白(High density lipoprotein,HDLC)水平显著高于正常对照组(P<0.05); 观察组脑卒中患者的microRNA133b中SNP+112A/T基因在A位点的基因频率显著高于正常对照组(P<0.05); microRNA133b的水平与血清LDLC的水平呈显著正相关(r=0.7,P<0.05)。结论 microRNA133b位点的单核苷酸位点基因多态性以及患者血清血脂代谢的紊乱可能都是脑卒中发生的重要影响因素,microRNA133b位点的单核苷酸位点基因多态性位点可能是脑卒患者潜在的分子标记物。     

No evidence for an association between the Glu298Asp polymorphism of the NOS3 gene and Alzheimer's disease

Summary. Recently a significant association of a missense mutation (Glu298Asp) of the endothelial nitric oxide synthase (NOS3) gene with late-onset Alzheimer's disease (LOAD) was reported. We tried to replicate this finding in a Japanese sample of 121 patients with LOAD, 51 with early-onset AD (EOAD), and 165 medical controls. However, the genotype and allelic distributions for the Glu298Asp polymorphism were similar for these three groups, suggesting that the Glu298Asp polymorphism of the NOS3 gene has no relevance to the development of AD in Japanese. Received March 20, 2000; accepted May 22, 2000     

miRNA-146a基因多态性与婴儿痉挛的相关性

目的 探讨我国中部地区汉族人群中miR-146a基因SNP位点(rs2910164和rs57095329)多态性与婴儿痉挛易感性的关系.方法 采用病例对照研究方法,选取在武汉大学人民医院儿科188例婴儿痉挛患者为研究组,选取同期体检的健康儿童214名为对照组.利用PCR-RFLP方法检测rs2910164和rs57095329两个SNP位点的多态性分布.结果 miR-146a基因SNP位点rs57095329基因型(GG、AG、AA)频率分布和G等位基因频率与对照组比较,差异均有统计学意义(P＜0.05),但该位点基因频率与婴儿痉挛发作频率无相关性(P＞0.05).SNP位点rs2910164的基因型(CC、CG、GG)频率和等位基因C与对照组比较,差异均无统计学意义(P＞0.05).结论 位于miR-146a启动子区域的SNP位点rs57095329的多态性与婴儿痉挛的发病相关,但与其发作频率无相关性;而SNP位点(rs2910164)与婴儿痉挛的易感性不相关.     

硫氧还原蛋白结合蛋白基因多态性与精神分裂症的关联分析

目的探索硫氧还原蛋白结合蛋白（TXNIP）基因与精神分裂症的关联关系。方法以182个精神分裂症核心家系为研究对象,应用聚合酶链反应和限制性片段长度多态性技术（PCR-RFLP）对TXNIP基因标签单核苷酸多态性（htSNP）rs9245进行基因分型;使用传递不平衡（TDT）、基于单体型的单体型相对危险度分析（HHRR）检测TXNIP基因与精神分裂症之间的关联关系。结果①患者组、父母组htSNP rs9245位点各基因型的分布均符合Hardy-Weinberg平衡法则（矿值分别为0．68,0．02,df=1,P〉0．05）;②单体型相对风险分析（HHRR）显示htSNP rs9245位点等位基因在患者组和父母组的频数分布为χ^2=3．42,P=0．064;③传递不平衡检验（TDT）分析显示,杂合子父母传递给受累子女与非传递等位基因频率分布为χ^2=3．40,P=0．065,虽然差异未达到显著性,但接近边缘显著性。结论本研究虽未发现TXNIP基因htSNP rs9245与精神分裂症的发生存在关联,但不能排除两者的阳性关联,尚需选择更多SNP及扩大样本量进一步分析。     

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。     

No genetic association between polymorphisms in the kainate-type glutamate receptor gene, GRIK4, and schizophrenia in the Chinese population

BACKGROUND: Schizophrenia is a chronic psychiatric disorder with a strong genetic component. Several studies have suggested that dysfunctions in the glutamatergic transmission are linked to the pathogenesis of schizophrenia, and that the kainate ionotropic glutamate receptors are involved in this mechanism. A recent study provides cytogenetic and genetic evidence to support a role for the kainate-type glutamate receptor gene (GRIK4), in schizophrenia. A systematic case-control association study of GRIK4 involving a Scottish population found that three SNPs, rs4935752, rs6589846 and rs4430518, were associated with schizophrenia. METHODS: Here, we investigated rs4935752, rs6589846, rs4430518 and other 2 SNPs within the GRIK4 gene in an association study of the Chinese population. Our sample consisted of 288 schizophrenia and 288 control subjects. All recruits were Han Chinese drawn from the city of Shanghai. RESULTS: No individual SNP nor any haplotype was associated with schizophrenia in our study. CONCLUSION: These results suggest that the five SNPs within the GRIK4 gene are unlikely to play a major role in the susceptibility to schizophrenia in the Chinese population.     

DNA修复基因XRCC1多态性与颅底脑膜瘤易感性关联研究

目的探讨DNA修复基因XRCC1单核苷酸多态性(SNP)与颅底脑膜瘤易感性的关系。方法采用病例-对照研究方法,收集124例颅底脑膜瘤患者和218例健康对照,运用多重单碱基延伸SNP分型(Multiplex SNa Pshot)技术检测XRCC1基因rs1799782位点在脑膜瘤组和对照组中的分布情况。结果 XRCC1 rs1799782位点中CT基因型携带者患颅底脑膜瘤的风险降低(OR=0.606,95%CI:0.374~0.982,P=0.041)。在颅底脑膜瘤组中,≥50岁组相比50岁组的个体,其发病风险降低(OR=0.4160,95%CI=0.201~0.862)。XRCC1基因rs1799782多态性与颅底脑膜瘤的生长部位、瘤周水肿、骨质破坏及硬膜侵袭之间不存在关联性(P0.05)。结论 XRCC1基因rs1799782位点CT基因型携带者可降低颅底脑膜瘤发病风险,rs1799782多态位点可能与颅底脑膜瘤发病风险相关,相对低龄患者更容易发病,但仍需大样本量的颅底脑膜瘤流行病学研究加以证实。     

中国人ApoE基因多态性与血管性痴呆关系的Meta分析

目的评价我国人群ApoE基因多态性与血管性痴呆的关系。方法对1996年1月至2011年5月公开发表的关于中国人血管性痴呆ApoE基因多态性的病例对照研究进行Meta分析。结果共纳入20个病例对照研究。Meta分析结果表明,中国人携带ε4等位基因的个体发生血管性痴呆的危险性的合并OR值为2.20[95%CI(1.81,2.66)];中国汉族人携带ε4等位基因的个体发生血管性痴呆的危险性的合并OR值为3.11[95%CI(2.06,4.69)]。结论载脂蛋白E基因多态性与中国人血管性痴呆相关,携带ε4等位基因的个体有发生血管性痴呆的倾向。     

The Ser9Gly polymorphism of the dopamine D3 receptor gene and risk of schizophrenia: an association study and a large meta-analysis

Dopamine D3 receptor (DRD3) binds antipsychotic drugs and is abundant in the limbic system of the brain. It has been shown to play important roles in schizophrenia. A number of studies investigated the Ser9Gly polymorphism of the DRD3 gene to test its possible association with schizophrenia; however, the results were inconsistent. Our study aims to further evaluate the possible association between the Ser9Gly polymorphism and schizophrenia using a case-control association study within the Han Chinese population as well as a meta-analysis covering all previous studies. Our study, based on 329 schizophrenic patients and 288 controls, found no significant difference in the genotype or allele distributions of Ser9Gly polymorphism, the meta-analysis showed that the Ser9Gly polymorphism was not associated with Schizophrenia. Our study does not support the contention that the Ser9Gly polymorphism of the DRD3 gene plays a major role in schizophrenia in the Chinese population.