肿瘤坏死因子TNF-α基因多态性与精神分裂症易感性关系的Meta分析

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刘军, 虞洪, 顾宝罗, 贺超奇. 肿瘤坏死因子TNF-α基因多态性与精神分裂症易感性关系的Meta分析. 2011, 26(5): 306-311
LIU Jun, YU Hong, GU Baoluo, HE Chaoqi. Meta analysis on the association of polymorphisms of tumor necrosis factor-alpha gene with schizophrenia risk. Labratory Medicine, 2011, 26(5): 306-311 复制到剪切板

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肿瘤坏死因子TNF-α基因多态性与精神分裂症易感性关系的Meta分析

刘军¹, 虞洪², 顾宝罗¹, 贺超奇¹

1.杭州师范大学医学院附属萧山第一医院检验科,浙江杭州 311201

2.浙江省萧山医院精神卫生中心,浙江杭州 311201

作者简介：刘军,男,1972年生,硕士,副主任技师,主要从事分子诊断学检验工作。

基金:杭州市萧山区科技局项目(2008078);

摘要

目的

有越来越多的证据表明精神分裂症和肿瘤坏死因子α(TNF-α)基因的多态性存在关联,但是许多研究的结果常常是相互矛盾的,因此,我们通过Meta分析的方法来评价TNF-α位点(-308、-238、-857和-1031)多态性和精神分裂症易感性之间的关系。

方法

检索PubMed和中国学术期刊网数据库,使用的关键词包括schizophrenia、TNF a、tumor necrosis factor a、tumor necrosis factor alpha、TNF alpha、多态性、肿瘤坏死因子和精神分裂症。检索时间为1989至2010年公开发表的期刊论文。以比数比(OR)及其 95%可信区间(95%CI)为效应尺度。

结果

按照纳入标准,共有13篇文献最终进入系统。Meta分析结果表明,-308多态性和精神分裂症不存在明显关联(G/A等位基因:合并OR=1.06,95%CI为0.79~1.42,P=0.71),-308的基因型分布在病例与对照之间亦无明显差异,亚组分析显示,无论是在高加索人种还是亚洲人种中,-308多态性与精神分裂症之间并无明显相关性。对于-238、-857和-1031几个多态性位点的Meta分析,亦未发现与精神分裂症易感性之间存在相关性。

结论

TNF-α位点(-308、-238、-857和-1031)的多态性和精神分裂症不存在明显关联。

关键词: 肿瘤坏死因子α; 精神分裂症; 多态性; Meta分析

中图分类号:Q503 文献标志码:A 文章编号:1673-8640(2011)05-0306-06

Meta analysis on the association of polymorphisms of tumor necrosis factor-alpha gene with schizophrenia risk

LIU Jun¹, YU Hong², GU Baoluo¹, HE Chaoqi¹

1.Department of Clinical Laboratory, Xiaoshan First Hospital Affiliated to Hangzhou Normal University School of Medicine, Zhejiang Hangzhou 311201, China

2. Mental Health Center, Xiaoshan Hospital, Zhejiang Hangzhou 311201, China

Fund:

Abstract

Objective

Objective An increasing amount of evidence suggests that the schizophrenia is associated with the polymorphisms of tumor necrosis factor-alpha (TNF-α) gene. However, the results of different studies are often inconsistent. So, to investigate the association of TNF-α polymorphisms (-308,-238,-857 and -1031) with schizophrenia risk by Meta analysis.

Methods

Studies and thesises published from 1989 to 2010 were searched through PubMed by the keywords: schizophrenia, TNF a, tumor necrosis factor a, tumor necrosis factor alpha and TNF alpha, and through CNKI by the keywords 多态性(polymorphism), 肿瘤坏死因子(tumor necrosis factor-alpha) and 精神分裂症(schizophrenia). The results were expressed as odds ratios (OR) and their 95% confidence intervals (CI).

Results

13 studies were found. The results by Meta analysis suggested no significant association between -308 polymorphism and schizophrenia risk (G/A allele: pooledOR=1.06, 95%CI=0.79-1.42,P=0.71). No significant difference in genotype distribution of -308 polymorphism in schizophrenia was found. Subgroup analysis also showed that there was no correlation between the populations of Caucasian and Asian. For the -238,-857 and -1031 polymorphisms, Meta analysis showed no correlation with schizophrenia risk.

Conclusions

There is no significant correlation between TNF-α polymorphisms (-308, -238, -857 and -1031) and schizophrenia risk.

Keyword: Tumor necrosis factor-alpha; Schizophrenia; Polymorphism; Meta analysis

Show Figures

精神分裂症是常见且严重的精神疾病之一,其病因未明。越来越多的证据表明,细胞因子在精神分裂症的病因和发病机制中起重要作用。肿瘤坏死因子(tumor necrosis factor,TNF)是一种多功能的炎症前细胞因子,主要由单核——巨噬细胞产生的TNF-α和活化的T淋巴细胞产生的TNF-β组成。成熟的TNF-α含有157个氨基酸,具有广泛的生物学活性,参与机体的细胞和体液免疫并参与调节神经元和胶质细胞的生长、分化和凋亡。在中枢神经元和胶质细胞都可以合成和分泌TNF-α,外周TNF-α可通过血脑屏障直接进入中枢神经系统,产生中枢效应^{[ 1]}。TNF-α对单胺类神经元既有神经保护作用又有神经毒性作用,并影响神经细胞的生长、增殖和分化。有一些研究表明精神分裂症患者血液中TNF-α的浓度显著高于正常对照^{[ 2~ 4]}。近年来研究显示TNF基因具有多态性。TNF-α的基因多态性主要表现为-G308A、-G238A、-G276A、-G163A、 -T1031C、-C863A、-C857T和-G70A等位点的碱基变异。Boin等^{[ 5]}2001年首先报道了TNF-α基因的-G308A多态性与精神分裂症存在关联。目前对TNF-α与精神分裂症关系方面的研究主要集中在-G308A位点,另外还有-G238A、-T1031C、-C863A和-C857T等位点。目前国内外已有多项关于TNF-α基因多态性与精神分裂症易感性关系的研究,但各研究结果不尽一致,且多是小样本量研究。Meta分析是系统评价中采用定量合成的方法对资料进行统计学处理从而得出的合并效应量的过程。本研究对TNF-α基因多个位点的多态性与精神分裂症易感性关系进行Meta分析。

材料和方法

一、文献的收集

检索PubMed和中国学术期刊网数据库,以得到TNF-α基因单核苷酸多态性(SNP)和精神分裂症易感性关系的所有病例对照研究。使用的关键词包括schizophrenia、TNF a、tumor necrosis factor a、tumor necrosis factor alpha、TNF alpha、多态性、肿瘤坏死因子和精神分裂症。检索时间为1989至2010年公开发表的期刊论文。同时也采用了文献追溯的方法。纳入文献标准:(1)采用病例-对照设计;(2)有各种基因型频率的数据;(3)对照研究资料的基因型频率分布满足Hardy-Weinberg平衡;(4)病例为精神分裂症患者,对照组与病例组间性别差异无统计学意义;(5)文献中基因型数据与先前发表的文献无重复。

二、数据提取

由 2 名独立的研究者对入选文献的数据进行录入并核对,摘录的主要内容包括研究者姓名、发表杂志和年份、病例和对照者的数量、等位基因及基因型的分布频率等。如同一个研究报告中涉及相同的人群,则每一个人群均以单独的研究入选。如一组人群的研究以不同的形式或语言发表在不同杂志,则选择其中数据资料最完整的研究纳入。为确保尽可能多的研究入选以增加 Meta 分析的可信性,部分资料缺失的研究,通过与研究者之间进行联系以补充完善。

三、统计学方法

以比数比(odds ratio, OR)及其 95%可信区间(confidence interval, 95% CI)评价基因多态性与精神分裂症之间的关联强度。在每个研究中,分别对病例组和对照组内等位基因的频率、基因型分布情况进行分析,在评估致病基因的效能时,不仅对其纯合子的致病风险进行评估,同时也对其携带者(杂合子和纯合子)相对于野生型纯合子的致病风险进行评估。应用 Meta 分析软件包 Revman 5 软件进行数据整理和分析,对各文献结果进行一致性检验,并根据检验结果选用相应的数据合并方法,若各研究间无显著异质性,则采用 Mantel-Haenszel固定效应模型进行数据合并,若结果间存在显著异质性,则采用随机效应模型进行数据合并,计算总 OR值。

结果

一、文献检索结果

按照纳入标准,最后进入本次系统评价进行Meta分析的文献共有13篇^{[ 5~ 17]},原始数据见表1。其中13篇文献^{[ 5~ 17]}涉及-G308A多态性的研究,累计精神分裂症病例2 852例,对照组3 285例;4篇文章^{[ 7, 12, 14, 17]}涉及-G238A多态性的研究,累计精神分裂症病例1 075例,对照组1 192例;3篇文章^{[ 7, 14, 17]}涉及-C857T多态性的研究,累计精神分裂症病例823例,对照组1 035例;3篇文章^{[ 7, 14, 17]}涉及-T1031C多态性的研究,累计精神分裂症病例823例,对照组1 038例。3篇文章^{[ 7, 14, 17]}对4个位点多态性与精神分裂症的关系均进行了分析,1篇文章^{[ 12]}同时对-G308A与-G238A多态性与精神分裂症的关系进行了分析。入选13篇文章分别来自美国、德国、意大利、巴西、波兰、芬兰、韩国、日本、新加坡和中国等国家,涉及高加索人和亚洲人2个人种。

表1 有关-G308A基因多态性与精神分裂症相关性入选研究的基本情况

二、Meta分析

1.TNF-α -G308A多态性与精神分裂症的关系同质性检验以及合并后 OR值列表于表2。在-G308A多态性有关的研究中,各个个体研究的结果之间存在显著的异质性,总体而言,-G308A多态性与精神分裂症之间无明显的相关性,见表2和图1。亚组分析显示,当将13个入选研究分为亚洲人和高加索人2个亚组分析时发现,在亚洲人种当中,A等位基因、AA基因型、GA基因型和GG基因型均与精神分裂症之间无明显相关性,在高加索人种中,亦未发现-G308A多态性与精神分裂症存在明显相关性,见表2和图1。

表2 TNF-α -G308A多态性与精神分裂症关系Meta分析结果

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	图1 TNF-α -G308A A等位基因相对于G等位基因精神分裂症易感性Meta分析森林图

2. TNF-α -G238A多态性与精神分裂症的关系共有4个病例-对照研究涉及到TNF-α -G238A多态性与精神分裂症的关系,3例是在亚洲人群中进行的研究,1例涉及到高加索人种。Meta分析结果显示突变纯合子AA基因型和精神分裂症不存在相关性。由于突变纯合子AA的基因频率非常低,故将其归入杂合子GA基因型组,结果显示AA+GA基因型与精神分裂症亦不存在相关性。

3. TNF-α -C857T与精神分裂症的关系共有3个病例-对照研究涉及到TNF-α -C857T多态性与精神分裂症的关系,2例是在亚洲人群中进行的研究,1例涉及到高加索人种。Meta分析结果显示突变纯合子TT基因型和精神分裂症不存在相关性。将突变纯合子TT归入杂合子CT基因型组,结果显示TT+CT基因型与精神分裂症亦不存在相关性。

4. TNF-α-T1031C多态性与精神分裂症的关系共有3个病例-对照研究涉及到TNF-α -T1031C多态性与精神分裂症的关系,2例是在亚洲人群中进行的研究,1例涉及到高加索人种。Meta分析结果显示突变纯合子CC基因型和精神分裂症不存在相关性。将突变纯合子CC归入杂合子TC基因型组,结果显示CC+TC基因型与精神分裂症亦不存在相关性。具体数值见表3。

表3 TNF-α -G238A、-C857T及-T1031C多态性与精神分裂症关系Meta分析结果

总而言之,Meta分析结果表明,TNF-α基因SNP位点-238、-857及-1031的多态性与精神分裂症不存在相关性。

讨论

本研究对有关TNF-α基因-G308A、-G238A、-C857T和-T1031C多态性与精神分裂症相关性的文献进行了Meta分析,结果显示上述4个SNP位点的多态性与精神分裂症不存在明显的相关性。

在这几个SNP位点当中,-G308A研究得最为广泛。Boin等^{[ 5]}首先发现A等位基因在病例中出现的频率显著高于对照,随后陆续有一些研究证实-G308A的多态性与精神分裂症之间存在关联。但是,其他的一些研究则表明-G308A的多态性与精神分裂症不存在相关性。在此基础之上,Sacchetti等^{[ 18]}收集了12篇文献,对-G308A的多态性与精神分裂症之间的关系作了Meta分析,共涉及到病例2 512例,对照3 223例,他们的研究结果表明,-G308A的多态性与精神分裂症之间无明显的相关性,但在高加索人群中,AA基因型和精神分裂症存在微弱的相关性( OR=1.65,95% CI为1.00~2.71, P=0.05)。我们收集了13篇文献,涉及病例2 852例,对照3 285例。我们发现,不仅-G308A的多态性与精神分裂症之间不存在相关性,而且在高加索人群中,亦未发现AA基因型和精神分裂症存在明显相关性。尽管已有研究表明,TNF-α可能在精神分裂症的发病机制中占有一定的作用,且-308位点的多态性可直接影响TNF-α的表达,但是,目前精神分裂症发病的分子机制并不十分清楚,各种炎症细胞因子基因不同位点的多态性与精神分裂症的易感性之间的关系亦有不同的结果,同时由于地区人种差异、个体差异及检测方法的不同,造成了目前炎症细胞因子基因多态性与精神分裂症易感性的研究中存在着不同甚至矛盾的结果。Meta分析是对具有相同研究目的且相互独立的多个研究结果予以合并作出定量分析。通过合并多个同类研究,达到增大样本量,提高检验效能的目的,经正确方法建立起来的Meta分析结果一般来说更接近真实情况,在医学领域内的决策评价方面具有独特的作用。但是统计学上的合并也不可避免地带来许多混杂因素,其中最突出的就是发表的偏倚性。这些因素的存在会在一定程度上影响到Meta分析的合并效应量的可靠性。因此开展更多设计合理的随机对照研究,将研究结果纳入Meta分析以解决这一问题。我们将密切关注这一方面的研究进展,将更多的研究结果纳入我们的分析系统,以便对TNF-α基因多态性与精神分裂症的关系作一个更加合理、可靠的结论。

对于-G238A、-C857T和-T1031C多态性与精神分裂症相关性,由于发表的文献比较少,我们只能作出一个初步的结论,这些位点多态性与精神分裂症是否存在相关性,还需进行更多的研究,能有更多的研究结果纳入我们的分析系统进行分析,才能得出一个可靠、科学的结论。

The authors have declared that no competing interests exist.

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2006

0.0

... 可通过血脑屏障直接进入中枢神经系统,产生中枢效应^[1] ...

2001

4.59

0.0

... 的浓度显著高于正常对照^[2~4] ...

1997

2.456

0.0

2001

4.59

0.0

... 的浓度显著高于正常对照^[2~4] ...

2001

14.897

0.0

. 2000, 6(1):-

Association between |[minus]|G308A tumor necrosis factor alpha gene polymorphism and schizophrenia

Molecular Psychiatry publishes work aimed at elucidating biological mechanisms underlying psychiatric disorders and their treatment

... Boin等^[5]2001年首先报道了TNF-#cod#x003b1 ...

... 结果一、文献检索结果按照纳入标准,最后进入本次系统评价进行Meta分析的文献共有13篇^[5~17],原始数据见表1 ...

... 其中13篇文献^[5~17]涉及-G308A多态性的研究,累计精神分裂症病例2 852例,对照组3 285例 ...

... Boin等^[5]首先发现A等位基因在病例中出现的频率显著高于对照,随后陆续有一些研究证实-G308A的多态性与精神分裂症之间存在关联 ...

2008

0.0

2004

2.026

0.0

. 2004, 366(2):null-null

No association between the promoter variants of tumor necrosis factor alpha (TNF-alpha) and schizophrenia in Chinese Han population

... 4篇文章^[7,12,14,17]涉及-G238A多态性的研究,累计精神分裂症病例1 075例,对照组1 192例 ...

... 3篇文章^[7,14,17]涉及-C857T多态性的研究,累计精神分裂症病例823例,对照组1 035例 ...

... 3篇文章^[7,14,17]涉及-T1031C多态性的研究,累计精神分裂症病例823例,对照组1 038例 ...

... 3篇文章^[7,14,17]对4个位点多态性与精神分裂症的关系均进行了分析,1篇文章^[12]同时对-G308A与-G238A多态性与精神分裂症的关系进行了分析 ...

2005

2.026

0.0

. 2005, 385(1):null-null

Tumor necrosis factor-alpha-G308A polymorphism in schizophrenia in a Finnish population

2004

3.052

0.0

. 2004, 111(2):217-221 DOI:10.1007/s00702-003-0101-z

Association analysis of the -308G #cod#x0003E; A promoter polymorphism of the tumor necrosis factor alpha (TNF-alpha) gene in Japanese patients with schizophrenia

1.Department of Mental Disorder Research National Institute of Neuroscience, National Center of Neurology and Psychiatry Tokyo Japan 2.Department of Psychiatry Nagoya University Graduate School of Medicine Nagoya Japan 3.Department of Psychiatry Fujita Health University School of Medicine Nagoya Japan 4.Department of Psychiatry Showa University School of Medicine Tokyo Japan

Two research groups have thus far reported a significant association between schizophrenia and a promoter polymorphism (–308G > A) of the gene encoding tumor necrosis factor alpha (TNF- ), while contradictive negative results have also been reported. We examined the possible association in a Japanese sample of 297 schizophrenia cases and 458 controls. Allele frequencies of both the patients and controls were very low (1.5% and 0.8%, respectively), and the difference was not statistically significant. We conclude that the effect of the –308G > A polymorphism on the development of schizophrenia is, if any, weak and the majority of Japanese schizophrenics are unrelated to the –308G > A polymorphism of the TNF- gene.

2005

3.2

0.0

. 2005, 255(4):279-283 DOI:10.1007/s00406-004-0560-8

Interaction of tumor necrosis alpha-G308A and epidermal growth factor gene polymorphisms in early-onset schizo-phrenia

1.University of Tampere Medical School 33014 Tampere Finland 2.Sein?joki Hospital District Department of Psychiatry 60220 Sein?joki Finland 3.Kanta-H?me Central Hospital Department of Psychiatry 13530 H?meenlinna Finland 4.Laboratory of Atherosclerosis Genetics Department of Clinical Chemistry Centre for Laboratory Medicine Tampere University Hospital Teiskontie 35 PL 2000 33521 Tampere Finland 5.Tampere University Hospital Department of Psychiatry 33380 Pitk?niemi Finland

The study population comprised 94Finnish patients with DSM-IV diagnosis of schizophrenia.The patients were placed into two subgroups accordingto medication response to conventional neuroleptics.The aim of the study was to examine thefrequency of tumor necrosis factor – 308 (G > A) polymorphismin these patients and their 98 control subjectswho were age– and gender–matched blood donors. Associationsbetween TNF α – 308 polymorphism alone andbetween the interaction of TNF α and epidermal growthfactor gene polymorphisms, and medication responseand age at onset of schizophrenia were also studied. Thefrequencies of TNF α A–allele were 11.7 % in patients and12.8% in controls. The difference was not significant(p = 0.75). TNF α – 308 polymorphism was not associatedwith medication response. However, patients with EGFAA and TNFα AG/AA genotype had a lower age at onsetof schizophrenia compared with the rest of the patientsnot having this combination (20.0 years, 3.3 vs. 30.2years, 10.1 mean + SD; p TNF α polymorphismis not associated with the incidence of schizophrenia.On the other hand, the role of cytokines inschizophrenia may involve genetic interactions predisposingearly onset of illness.

2003

2.04

0.0

. 2003, 57(4):399-403

Tumor necrosis factor-α gene polymorphism at position −308 and schizophrenia in the Korean population

Chi-Un Pae , MD 1 ,Jeong-Ho Chae , MD, PhD 2 ,Won-Myong Bahk , MD, PhD 2 ,Hoon Han , MD, PhD 3 ,Tae-Youn Jun , MD, PhD 2,* ,Kwang-Soo Kim , MD, PhD 2 ,Yong-Sil Kwon , MD, PhD 4 andAlessandro Serretti , MD 5

1 Department of Psychiatry, Kangnam St Mary's Hospital, Catholic University of Korea College of Medicine, Seocho-Gu, 2 Department of Psychiatry, St Mary's Hospital, Catholic University of Korea College of Medicine, Youngdeungpo-Gu, 3 Department of Microbiology and Immunology, Catholic University of Korea College of Medicine, Seoul, 4 Department of Psychiatry, Uijongbu St Mary's Hospital, Catholic University of Korea College of Medicine, Kyonggido, Korea and 5 Department of Psychiatry, Vita-Salute University, San Raffaele Institute, Milan, Italy * Tae-Youn Jun, Department of Psychiatry, Uijongbu St Mary's Hospital, Catholic University of Korea College of Medicine, 62 Yoido-Dong, Youngdeungpo-Gu, Seoul 150-713, Korea. Email: tyjun@cmc.cuk.ac.kr

> Abstract The purpose of the present study was to examine the association between the tumor necrosis factor (TNF)-α gene (A) polymorphism and schizophrenia in a Korean sample of schizophrenic patients and control subjects. Genotyping for the TNFA polymorphism was performed by polymerase chain reaction–restriction fragment length polymorphism. Genotype and allele distributions of the TNFA polymorphism between schizophrenic patients and controls were not significantly different. In the light of these results, the TNFA polymorphism seems not to confer susceptibility to the pathogenesis of schizophrenia, at least in the Korean population.

2006

3.052

0.0

. 2006, 113(7):887-897 DOI:10.1007/s00702-005-0358-5

Interaction analysis between 5-HTTLPR and TNFA-238/-308 polymorphisms in schizophrenia

1.College of Medicine, The Catholic University of Korea, Kangnam St. Mary’s Hospital, Banpo-Dong, Seocho-Gu Department of Psychiatry Seoul Korea Seoul Korea 2.University of Milan, School of Medicine Department of Neurosciences, Istituto Scientifico H San Raffaele Milan Italy Milan Italy

This study investigated the potential interaction between the polymorphisms of serotonin transporter gene ( SLC6A4 , a 44 base pair insertion/deletion in the promoter region, 5-HTTLPR) and tumor necrosis factor-α gene ( TNFA ; −238G/A and −308G/A polymorphisms) on the development of schizophrenia, as well as the interaction of the three polymorphisms in relation to symptomatology, family history, onset age and antipsychotic treatment response. Genomic DNA analyses with polymerase chain reaction (PCR) was used for the genotyping. One hundred and fifty-two (152) patients with schizophrenia and 152 normal controls participated in the study. Any associations between the individual polymorphism and schizophrenia were not found. However, marginal association between subjects with both TNFA −238 A allele (genotype AA plus AG) and 5-HTTLPR s allele ( ss plus sl ) and presence of family history was found (p = 0.023; p = 0.026). The subjects with TNFA −308 AG genotype showed higher change in PANSS total score (p = 0.028). No significant interaction effect between 5-HTTLPR and TNFA −238/−308 polymorphisms either on the development of schizophrenia or on antipsychotics treatment response and psychopathology was found, although a significant interaction effect for subjects carrying TNFA −238 AG and −308 AA genotypes on a positive family history was observed (p = 0.017). These results suggest that the interaction effects between 5-HTTLPR and TNFA −238/−308 polymorphisms gives no significant contribution to the susceptibility to schizophrenia, and is not associated with clinical variables, antipsychotic treatment response and psychopathological features, except for family history of disease, at least in the Korean population.

... 4篇文章^[7,12,14,17]涉及-G238A多态性的研究,累计精神分裂症病例1 075例,对照组1 192例 ...

... 3篇文章^[7,14,17]对4个位点多态性与精神分裂症的关系均进行了分析,1篇文章^[12]同时对-G308A与-G238A多态性与精神分裂症的关系进行了分析 ...

2002

3.2

0.0

. 2002, 252(5):232-234 DOI:10.1007/s00406-002-0386-1

No association between the G308A polymorphism of the tumor necrosis factor-alpha gene and schizophrenia

1.Psychiatric Hospital, Ludwig-Maximilian University Munich, Nussbaumstr. 7, 80336 Munich, Germany. mschwarz@psy.med.uni-muenchen.de DE 2.Psychiatric Hospital, University of Bonn, Bonn, Germany DE

Several linkage analyses in schizophrenia research point to a locus on chromosome 6p22, where the gene coding for tumor necrosis factor-α (TNF-α) is located. A marked influence of antipsychotic medication on TNF-α has been described. As the involvement of an immune process in the pathophysiology of schizophrenia has been discussed, a functional TNF-α polymorphism appears to be a candidate in genetic schizophrenia research. The G308A polymorphism of the TNF-α gene was described to be associated with increased TNF-α production. Boin and colleagues have already described a significant association between the polymorphic allele and schizophrenia, investigating 84 schizophrenic patients (21 % polymorphic allele) and 138 healthy volunteers (11 % polymorphic allele), recruited in Northern Italy.

2006

4.59

0.0

... 4篇文章^[7,12,14,17]涉及-G238A多态性的研究,累计精神分裂症病例1 075例,对照组1 192例 ...

... 3篇文章^[7,14,17]涉及-C857T多态性的研究,累计精神分裂症病例823例,对照组1 035例 ...

... 3篇文章^[7,14,17]涉及-T1031C多态性的研究,累计精神分裂症病例823例,对照组1 038例 ...

... 3篇文章^[7,14,17]对4个位点多态性与精神分裂症的关系均进行了分析,1篇文章^[12]同时对-G308A与-G238A多态性与精神分裂症的关系进行了分析 ...

2003

9.247

0.0

2003

4.59

0.0

2007

2.456

0.0

... 结果一、文献检索结果按照纳入标准,最后进入本次系统评价进行Meta分析的文献共有13篇^[5~17],原始数据见表1 ...

... 其中13篇文献^[5~17]涉及-G308A多态性的研究,累计精神分裂症病例2 852例,对照组3 285例 ...

... 4篇文章^[7,12,14,17]涉及-G238A多态性的研究,累计精神分裂症病例1 075例,对照组1 192例 ...

... 3篇文章^[7,14,17]涉及-C857T多态性的研究,累计精神分裂症病例823例,对照组1 035例 ...

... 3篇文章^[7,14,17]涉及-T1031C多态性的研究,累计精神分裂症病例823例,对照组1 038例 ...

... 3篇文章^[7,14,17]对4个位点多态性与精神分裂症的关系均进行了分析,1篇文章^[12]同时对-G308A与-G238A多态性与精神分裂症的关系进行了分析 ...

2007

5.612

0.0

. 2007, 21(4):450-457 DOI:10.1016/j.bbi.2006.11.009

-G308A tumor necrosis factor alpha functional polymorphism and schizophrenia risk: meta-analysis plus association study

Abstract Research on -G308A functional polymorphism in the tumor necrosis factor α (TNFα) gene as a susceptibility factor for schizophrenia has provided contrasting results in different populations. Therefore we conducted a meta-analysis of the published case–control association studies and a replication study in a large sample. Meta-analyses (total sample: 2512 cases versus 3223 controls) showed that the AA genotype was weakly associated with schizophrenia susceptibility in Caucasoids (Odd Ratio OR = 1.65, 95% CI = 1.00–2.71 Z = 1.98 p = 0.05). The replication case–control association study (323 DSM-IV-TR schizophrenia patients and 346 controls) showed that the A allele conferred an increased susceptibility for schizophrenia only in males (OR = 1.73, 95% CI = 1.07–2.79, p = 0.025), and the association became more specific when only patients of the paranoid subtype were compared to the controls (relative risk ratio = 3.09, 95% CI = 1.28–7.47, p = 0.012). The presence of the A allele was also associated with a later age at onset of schizophrenia in the whole sample ( F 1,291 = 7.094, p = 0.008). Our results confirm that TNFα A allele could have an effect on vulnerability to schizophrenia but further studies revaluating the role of gender and diagnostic subtypes are necessary to confirm these findings.

... 在此基础之上,Sacchetti等^[18]收集了12篇文献,对-G308A的多态性与精神分裂症之间的关系作了Meta分析,共涉及到病例2 512例,对照3 223例,他们的研究结果表明,-G308A的多态性与精神分裂症之间无明显的相关性,但在高加索人群中,AA基因型和精神分裂症存在微弱的相关性(OR=1 ...