中国新疆维吾尔族人群中ANK3基因rs10761482多态性与精神分裂症关联性的病例对照研究(英文)

背景:ANK3基因rs10761482多态性已被发现与精神分裂症的发生相关联。目的:评估新疆维吾尔族人群ANK3基因和精神分裂症之间的关联。方法:使用Taqman探针技术对630例新疆维吾尔族精神分裂症患者和535名新疆维吾尔族健康人群进行ANK3基因rs10761482位点的基因分型。采用SHEsis和SPSS17.0软件进行数据分析。结果:病例组和对照组之间的基因型和等位基因频率无显著差异。在病例组,性别或精神分裂症发病年龄与基因型或等位基因频率之间没有显著关联。将男性和女性单独分析,病例组与对照组之间的等位基因和基因型频率均未发现显著差异,青春期发病与成年后发病的精神分裂症患者之间的等位基因和基因型频率也无显著差异。结论:我们的研究结果不支持以往ANK3基因与精神分裂症有关联的报告。本研究招募的维吾尔族人群中,ANK3基因rs10761482多态性与精神分裂症之间没有显著关联。如果这些结果在进一步的研究中得到证实,那么研究重点将转而了解为什么在这个特定的族群中不存在上述已经被广泛认可的关联。     

烟碱型乙酰胆碱受体基因多态与早发性精神分裂症的关联研究

目的探讨烟碱型乙酰胆碱受体基因多态在早发性精神分裂症发生中的作用。方法采用TaqMan荧光探针基因分型技术对421例早发性精神分裂症患者和598例健康对照者的α3、α4、α7、α5烟碱型乙酰胆碱受体基因(nicotinic acetylcholine receptor subunit gene)即CHRNA3(rs1317286)、CHRNA4(rs1044396)、CHRNA7(rs6494212)及CHRNA5(rs16969968,rs684513)基因多态位点进行基因分型,分析这些位点与早发性精神分裂症的关联及其与发病年龄的关系,并进一步分析基因与基因的交互作用。结果单位点分析显示所有位点的差异比较结果无统计学意义。Kaplan-Meier生存分析显示携带rs1317286G等位基因的患者发病年龄晚于不携带rs1317286G等位基因的患者[发病年龄分别为(15.5±0.33)岁和(15.1±0.14)岁,P=0.010]。CHRNA5基因的两个单核苷酸多态位点(single nucleotide polymorphisms,SNPs)组成的单体型也显示不与早发性精神分裂症关联。进一步的基因交互作用分析显示rs1044396、rs6494212及rs684513联合作用模式可能与精神分裂症相关(P=0.0007)。结论 CHRNA3(rs1317286)位点可能与精神分裂症的发病年龄相关;rs1044396、rs6494212及rs684513基因的联合作用模式可能与早发性精神分裂症有关。     

NOS1AP基因rs348624多态性与中国汉族早发性精神分裂症的关联分析

目的:探讨中国汉族人群一氧化氮合酶1接头蛋白(NOS1AP)基因rs348624多态性与早发性精神分裂症的易感性及其首发年龄的关联性。方法:选取285例早发性精神分裂症患者为研究组和826名正常对照组,采用Taq Man法,检测NOS1AP基因rs348624位点多态性,并分析研究组危险等位基因的频率与首发年龄的关联性。结果:研究组与对照组rs348624等位基因和基因型频率分布比较差异有统计学意义[χ2=149.17,自由度(df)=1,P=0.00;χ2=137.25,自由度(df)=2,P=0.00];Kaplan-Meier分析显示,rs348624等位基因T的频率与早发性精神分裂症首发年龄显著相关(Kaplan-Meier log rank检验P=0.00)。结论:在中国汉族人群中NOS1AP基因与早发性精神分裂症存在关联,其rs348624多态性可能是导致早发性精神分裂症患者发病年龄提前的重要因素。     

DISC1基因rs821633位点多态性与中国汉族人群精神分裂症的相关性研究（英文）

背景:既往研究报告显示精神分裂症断裂基因1(Disrupted-in-Schizophrenia 1 gene,DISC1)中不同的单核苷酸多态性(single nucleotide polymorphisms,SNP)与精神分裂症密切相关,但目前尚无研究评估了SNP与精神分裂症发病年龄之间的关系。目的:探讨DISC1基因中rs821633位点的SNP和中国汉族精神分裂症患者的发病及首发年龄的相关性。方法:我们采用TaqM an基因分型技术对315例19岁之前发病的精神分裂症患者(即"早发性")、407例19岁后发病的精神分裂症患者(即"非早发性")和482名健康对照进行DISC1基因rs821633位点的SNP检测。我们使用生存分析研究rs821633(C)位点的危险等位基因与精神分裂症患者首发年龄之间的关系。结果:相比健康对照组,rs821633位点C/C基因型和C等位基因型频率分布在早发性(X~2=7.17,df=1,p=0.007;X~2=7.20,df=2,p=0.032)和晚发性(X~2=5.36,df=1,p=0.022;X~2=6.58,df=2,p=0.041)精神分裂症患者中显著较高。然而,C/C基因型或C等位基因型的携带率在早发和晚发性精神分裂症患者中没有显著差异。Kaplan-Meier生存分析发现rs821633(C)危险等位基因与精神分裂症首发年龄之间没有显著相关性。结论:我们证实了DISC1基因rs821633位点多态性的SNP与中国汉族人群精神分裂症之间存在相关性,但未发现rs821633(C)危险等位基因与精神分裂症首发年龄之间的相关性。     

精神分裂症锚蛋白重复序列3基因多态性及表达研究

目的探讨锚蛋白重复序列3(ankyrin repeat 3,ANK3)基因多态性和基因表达与精神分裂症的关系。方法采用Taq Man探针等位基因分型技术对456例中国汉族精神分裂症患者(患者组)和495名正常对照者(对照组)ANK3基因多态性位点rs10994336、rs10994359进行基因分型,并对基因型、等位基因、单体型频率进行比较;然后采用Taq Man探针及实时荧光定量PCR方法检测另外30例急性期精神分裂症患者和26名正常对照外周血ANK3基因m RNA的表达水平。结果患者组与对照组rs10994336和rs10994359基因型、等位基因频率分布的差异无统计学意义(P0.05)。单体型分析显示,由rs10994336-rs10994359组成单体型C-C、C-T、T-C的频率分布在患者组与对照组间差异无统计学意义(P0.05)。与对照组相比,急性期精神分裂症患者外周血ANK3基因的m RNA表达水平略高,但差异无统计学意义(P0.05)。结论本研究未发现ANK3基因位点rs10994336、rs10994359多态性与精神分裂症的关联,急性期精神分裂症患者外周血中ANK3基因的表达水平未见异常。     

COX-2基因多态性与帕金森病发病风险的相关性研究

目的探讨环氧化酶-2(COX-2)基因多态性与帕金森病(PD)发病风险的相关性。方法采用病例-对照研究方法,选取PD患者126例(PD组)和健康志愿者101例(对照组)。采用PCR-RFLP法检测两组COX-2基因rs20417、rs689466、rs689465及rs5275位点的多态性。结果与对照组比较,PD组rs20417等位基因G和C、rs689466等位基因G和A以及rs5275等位基因T和C分布频率,差异有统计学意义(P=0.012,P0.001,P=0.005)。携带rs20417等位基因C、rs689466等位基因G或rs5275等位基因C者患PD风险可能更高(显性模型OR=2.47,95%CI:1.33~4.59,P=0.004;OR=0.38,95%CI:0.16~0.88,P=0.025;OR=3.09,95%CI:1.47~6.48,P=0.003)。分层分析结果显示,早发PD组和晚发PD组rs689466基因型分布与对照组比较,差异有统计学意义(加性模型和隐性模型P0.05);rs20417和rs5275基因型分布在晚发PD组与对照组比较,差异有统计学意义(P=0.016和P=0.006)。结论江苏省南京地区汉族人群中COX-2基因rs20417、rs689466及rs5275位点多态性与PD发病风险具有一定相关性。     

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。     

精神分裂症伴发2型糖尿病与烟碱型乙酰胆碱受体基因多态性关联研究

目的在中国汉族精神分裂症患者中探讨烟碱型乙酰胆碱受体基因多态性与2型糖尿病共病的关联。方法采用Taq Man荧光探针基因分型技术对346例伴发2型糖尿病的中国汉族精神分裂症患者和360例不伴糖尿病的精神分裂症患者的α3、α4、α7、α5烟碱型乙酰胆碱受体(neuronal nicotinic acetylcholine receptor,n Ach R)基因即CHRNA3(rs1317286)、CHRNA4(rs1044396)、CHRNA7(rs6494212)及CHRNA5(rs16969968、rs684513)多态位点进行基因分型,比较等位基因频率和基因型频率,并进一步进行基因-基因交互作用分析。结果单位点分析显示男性患者rs6494212位点的等位基因分布和基因型分布在两组间差异均有统计学意义(P0.05);rs1317286、rs1044396、rs16969968、rs684513位点的基因型分布和等位基因分布均无明显差异(P均0.05)。CHRNA5基因的两个单核苷酸多态位点(single nucleotide polymorphisms,SNPs)组成的单体型与两组疾病共病关联无统计学意义(P0.05)。进一步基因交互作用分析显示rs131726、rs1044396、rs6494212及rs684513这4个位点的联合作用模式可能与两组疾病共病相关(P=0.002)。结论 CHRNA7(rs6494212)可能是中国汉族男性精神分裂症患者患2型糖尿病的易感基因。rs1317286、rs1044396、rs6494212及rs684513位点的联合作用可能与精神分裂症共病2型糖尿病相关。     

PPP1R3A基因多态性与中国维吾尔族人群精神分裂症关联性研究

目的探索蛋白磷酸酶1调节亚基3A(protein phosphatase 1 regulatory subunit 3A, PPP1R3A)基因外显子区域基因位点多态性与中国维吾尔族人群精神分裂症的关联性。方法利用多重PCR靶向捕获二代测序技术对528例维吾尔族精神分裂症患者及576名维吾尔族正常对照进行PPP1R3A基因外显子区域DNA扩增,Illumina HiSeq X Ten平台进行高通量测序,用阳性与阴性症状量表(positive and negative symptoms scale,PANSS)评估患者病情严重程度。结果患者组与对照组之间PPP1R3A基因rs1800000位点等位基因和基因型频率差异有统计学意义(P0.05);rs1799999位点基因型频率在女性患者组与对照组间差异有统计学意义(P0.05);rs8192686位点在男性患者组与对照组间等位基因频率差异有统计学意义(P0.05)。结论PPP1R3A基因rs1800000位点多态性可能与中国维吾尔族人群精神分裂症的发生发展存在关联性;rs1799999位点多态性可能与中国维吾尔族女性精神分裂症的发病有关联性;rs8192686位点C等位基因可能与中国维吾尔族男性精神分裂症发病有关联性。     

精神分裂症与多巴胺D4受体基因及载脂蛋白E基因的关联分析

目的　探讨上海地区汉族人群载脂蛋白E(apoE)基因、多巴胺D4 受体 (DRD4)基因与精神分裂症的易患性、患者的性别、发病年龄以及病程之间的关系。方法　应用聚合酶链反应扩增技术及限制性片段长度多态性对 80例精神分裂症患者和 80名正常人分别测定apoE、D4基因型和等位基因。结果　 (1 )患者组apoE等位基因ε2 频率明显高于对照组 ,与精神分裂症呈显著正关联 [相对危险度 (RR) =2 0 1 ,P <0 0 5] ;而且患者组男性等位基因ε2 频率明显高于对照组男性 ,与精神分裂症呈显著正关联 (RR =8 5l,P <0 0 5)。 (2 )DRD4基因与精神分裂症无关联 ,但是发病年龄与A2 ,A4等位基因及性别与 4/ 4基因型有关联 (P <0 0 5) ;(3)患者组与对照组携带ε4 与非携带ε4 间比较 ,DRD4基因的基因型和等位基因频率均无差异。患者组和对照组的组内携带ε4 与非携带ε4 间比较的差异均有显著性 ,对照组携带ε4 组的DRD4基因型 4/ 4 (85 % )和等位基因A4(89% )频率均明显高于非携带ε4组 (55 % ,67% ) ,而非携带ε4 组的等位基因A2 (2 9% )频率高于携带ε4 组 (1 2 % ) ;患者组非携带ε4 组的DRD4基因型 2 / 2 (1 3 % )和等位基因A2 (2 4 % )频率均高于携带ε4 组 (0 % ,8% )。结论　 (1 )apoE基因可影响精神分裂症患者的易患性     

Association of G72/G30 polymorphisms with early-onset and male schizophrenia

To explore the effect of G72/G30 polymorphisms on the clinical manifestations of schizophrenia, especially on the age at onset and sex of patients, we examined three single nucleotide polymorphisms in 216 schizophrenic patients and 321 healthy controls. Significant associations of schizophrenia with the A allele of rs947267 (P=0.012) and haplotype A-A-G (rs2391191-rs947267-rs778294) (P=0.008) were found in early-onset schizophrenic patients. So did the same allele (P=0.034) and haplotype (P=0.009) as mentioned above in male patients. These findings suggest that the G72/G30 gene may modulate the age at onset and there might be a potential interaction between this locus and sex in the pathogenesis of schizophrenia.     

ESPECTRA: Searching the Bipolar Spectrum in Eating Disorder patients

Background

Genome wide association studies reported two single nucleotide polymorphisms in ANK3 (rs9804190 and rs10994336) as independent genetic risk factors for bipolar disorder. Another SNP in ANK3 (rs10761482) was associated with schizophrenia in a large European sample. Within the debate on common susceptibility genes for schizophrenia and bipolar disorder, we tried to investigate common findings by analyzing association of ANK3 with schizophrenia, bipolar disorder and unipolar depression.

Methods

We genotyped three single nucleotide polymorphisms (SNPs) in ANK3 (rs9804190, rs10994336, and rs10761482) in a case-control sample of German descent including 920 patients with schizophrenia, 400 with bipolar affective disorder, 220 patients with unipolar depression according to ICD 10 and 480 healthy controls. Sample was further differentiated according to Leonhard's classification featuring disease entities with specific combination of bipolar and psychotic syndromes.

Results

We found no association of rs9804190 and rs10994336 with bipolar disorder, unipolar depression or schizophrenia. In contrast to previous findings rs10761482 was associated with bipolar disorder (p = 0.015) but not with schizophrenia or unipolar depression. We observed no association with disease entities according to Leonhard's classification.

Conclusion

Our results support a specific genetic contribution of ANK3 to bipolar disorder though we failed to replicate findings for schizophrenia. We cannot confirm ANK3 as a common risk factor for different diseases.     

SOX10 rs139883 Polymorphism Is Associated with the Age of Onset in Schizophrenia

Schizophrenia is a common psychiatric disorder with high heritability. The age of onset is an important phenotype of schizophrenia and may be under considerable genetic control. Our previous study showed that a single nucleotide polymorphism (SNP) rs139887 in sex-determining region Y-box 10 (SOX10) gene was associated with the age of onset in schizophrenia. The aim of this study was to evaluate the effect of another SNP rs139883 in the exon 4 of SOX10 on schizophrenia using an early-onset samples in the Han Chinese population. A total of 309 schizophrenic patients with onset before age 18 and 390 healthy controls were recruited for association study. No significant differences of allele or genotype frequencies were identified between the schizophrenic patients and controls. However, the C allele was significantly associated with an earlier age of onset in total patients and male patients (Kaplan–Meier log rank test P?=?0.026; Kaplan–Meier log rank test P?=?0.047, respectively), but not in females. In conclusion, the SOX10 rs139883 polymorphism influenced the age of onset of schizophrenia in a gender-specific manner and this may represent a vital genetic clue for the etiology of schizophrenia.     

Association of schizophrenia with the rs821633 polymorphism in the DISC1 gene among Han Chinese

Background

Previous studies report that various single nucleotide polymorphisms (SNP) in the Disrupted-in Schizophrenia 1 (DISC1) gene are closely associated with schizophrenia, but there are no studies that assess the relationship of age of onset of schizophrenia with these SNPs.

Objective

Investigate the relationship between the rs821633 SNP in the DISC1 gene and the occurrence and age of onset of schizophrenia in Han Chinese.

Methods

We used the TaqMan genotyping technology to examine the rs821633 SNP in the DISC1 gene among 315 individuals who developed schizophrenia prior to 19 years of age (‘early-onset’), 407 individuals who developed schizophrenia when 19 years of age or older (‘late-onset’), and 482 healthy controls. We used survival analyses to investigate the relationship between the rs821633(C) risk allele and the age of onset of schizophrenia.

Results

Compared to the prevalence in healthy controls, the prevalence of the C/C genotype of rs821633 and of the C allele in rs821633 were significantly greater in individuals with early-onset schizophrenia (X²=7.17, df=1, p=0.007; X²=7.20, df=2, p=0.032) and significantly greater in individuals with late-onset schizophrenia (X²=5.36, df=1, p=0.022; X²=6.58, df=2, p=0.041). However, there were no significant differences in the prevalence of the C/C genotype or the C allele between individuals with early-onset and late-onset schizophrenia. Kaplan-Meier survival analyses found no significant association between the rs821633(C) risk allele and age of onset in schizophrenia.

Conclusion

We confirm the association of polymorphism in the rs821633 SNP in the DISC1 gene with schizophrenia among Han Chinese, but we found no association between the rs821633(C) risk allele and the age of onset in individuals with schizophrenia.     

miR146a基因多态性与早发型阿尔茨海默病的关联性研究

目的 探讨miR146a的基因多态性与早发型阿尔茨海默病（EOAD）的关系.方法 本研究共纳入103例EOAD患者和100名健康对照组人群,采用SnapShot分型技术检测miR146a基因的rs2910164和rs57095329的多态性.结果 病例组的rs57095329位点的基因型和等位基因频率与健康对照组比较,差异有统计学意义（基因型P=0.027 0,等位基因频率P=0.004 2）,而rs2910164的病例组和对照组基因型和基因频率差异无统计学意义（基因型P=0.595 7,等位基因频率P=0.322 6）.结论 miR146a基因的rs57095329多态位点与EOAD的发病风险具有相关性,rs57095329的G等位基因是EOAD的发病风险的保护因素.     

Association between GABA-A receptor alpha 5 subunit gene locus and schizophrenia of a later age of onset

Heritability is considered to be a major etiologic factor for schizophrenia. Among the genes considered as candidates for the disease, are those related to GABAergic neurotransmission. Our aim was to test for a genetic association between GABA-A receptor alpha 5 subunit gene locus (GABRA(5)) and schizophrenia. Genotyping of the GABRA(5) locus was performed by the use of a dinucleotide (CA) repeat marker in 46 schizophrenic patients and 50 healthy individuals, all unrelated Greeks. Eight alleles were identified, 276-290 bp long. A nonsignificant excess of the 282-bp allele, which was found in a previous study in a Greek population to be associated with bipolar affective disorder, was observed in schizophrenic patients (33.8 vs. 23.9% in the controls). The frequency of this allele was 43.3% among patients with a later age of onset (over 25 years), differing at a statistically significant level from the controls (p < 0.05). These results suggest that common pathophysiological mechanisms may possibly underlie affective disorders and schizophrenia, at least in a subgroup of patients.     

Meta-analysis of association between PITX3 gene polymorphism and Parkinson's disease

Parkinson's disease (PD) is one of the most common neurodegenerative diseases. Several studies had researched the association between the PITX3 gene polymorphism and Parkinson's disease. However, the results were inconsistent. To evaluate whether PITX3 gene polymorphism is involved in the risk of PD we conducted this meta-analysis. All the eligible studies were searched from the databases of Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, MEDLINE, EMBASE, and Science Citation Index EXPANDED in any languages up to May 2011. Finally ten studies about PITX3 gene including 5172 patients and 7290 controls were identified for meta-analysis. Meta-analysis was carried out to evaluate whether PITX3 gene polymorphism was associated with PD, and subgroup analysis was also performed when necessary. This meta-analysis finds that rs4919621 allele A was significantly associated with PD in the Caucasian population (P=0.04,). Subgroup analysis of early onset PD (EOPD) and late onset PD (LOPD) revealed that the rs2281983 allele C and rs4919621 allele A were significantly associated with the risk of PD (all of the P values were ≤ 0.0001) in EOPD population. This research indicated that the presence of the rs4919621 allele A significantly increased the risk of PD patients in Caucasian population while rs2281983 allele C and rs4919621 allele A were both risk factors in EOPD.