注意缺陷多动障碍与儿茶酚-O-甲基转移酶基因的关联分析

目的：分析COMT基因多态性与ADHD的关联;寻找ADHD的易感基因。方法：采用PCR-RFLP技术,检测54名ADHD患者及其父母（n=82）和正常对照者（n=30）COMT基因Val158Met多态性的基因型和等位基因频率,运用病例对照研究和核心家系的关联分析（HRR和TDT）方法分别进行分析。结果：Val158Met多态性的各基因型和等位基因频率在ADHD组与对照组以及核心家系中的分布差异均无显著性（均P〉0．05）。注意缺陷为主型患儿COMT基因的G／G型频率和G等位基因频率明显高于混合型的（P〈0．05）,A等位基因与ADHD的某些临床症状如注意问题、违纪行为、攻击行为等相关。结论：（1）COMT基因可能与ADHD缺乏关联。仅起微效基因的作用：（2）COMT可能与ADHD临床亚型或临床症状有关。     

精神分裂症与儿茶酚氧位甲基转移酶基因多态性

分子遗传学的发展促进了精神分裂症的分子病因学研究。COMT作为多巴胺的主要代谢酶，在精神分裂症分子遗传学研究中具有重要地位。本文综述了精神分裂症的攻击行为、自杀、认知功能症状等与COMT基因的关系。     

精神分裂症与儿茶酚氧位甲基转移酶基因多态性

分子遗传学的发展促进了精神分裂症的分子病因学研究。COMT作为多巴胺的主要代谢酶,在精神分裂症分子遗传学研究中具有重要地位。本文综述了精神分裂症的攻击行为、自杀、认知功能症状等与COMT基因的关系。     

儿茶酚-O-甲基转移酶基因单核苷酸多态性位点与精神分裂症的关联研究

目的 探讨儿茶酚-O-甲基转移酶(catechol-O-methyl transferanse,COMT)基因8个单核苷酸多态性位点(single nRcleotide polymorphism,SNP)与粤东潮汕地区精神分裂症的关系.方法 应用聚合酶链式反应-聚丙烯酰胺凝胶芯片技术检测COMf基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)在粤东潮汕地区的279例精神分裂症患者和100名健康对照中的分布,并借助于plink软件对所得数据进行关联分析.结果 单个位点等位基因频率在两组间的分布差异无统计学意义;单倍型(G)-G-A-A[(rs4680)-rsl65599-rs2075507-rs6269]和单倍型A-A-C-(G)[rs2075507-rs6269-rs4633-(rs6267)]频率两组分布差异有统计学意义,精神分裂症组低于正常对照组,提示它们可能是精神分裂症的保护因素.结论 在中国粤东地区汉族人群中,COMT基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)与精神分裂症无关联性,其中的两个单倍型可能是精神分裂症的保护因素.但本研究不能排除COMT基因可能存在其他功能性变异位点与精神分裂症相关.

Abstract：

Objective To investigate the association between 8 polymorphisms in the catechol-O-methyl transferase gene (COMT) and schizophrenia in Yuedong-Chaoshan region of China. Methods Eight single nucleotide polymorphism (SNPs), namely rs4680, rs4818, rs165599, rs737865, rs2075507, rs6267,rs6269 and rs4633, in the COMT gene were genotyped in 279 schizophrenia patients and 100 healthy controls. Results There was no significant difference between any single SNP and schizophrenia.However, association might exist between haplotypes (G)-G-A-A [(rs4680) -rs165599-rs2075507-rs6269]and A-A-C-(G) [rs2075507-rs6269-rs4633-(rs6267)] and schizophrenia. Conclusion In the population of Yuedong region of China, the eight SNPs (rs4680, rs4818, rs165599, rs737865, rs2075507, rs6267,rs6269 and rs4633) in the COMT gene are unlikely to play a major role in the susceptibility to schizophrenia.There might be protective haplotypes in the COMT gene against schizophrenia.     

儿茶酚-O-甲基转移酶基因单核苷酸多态性位点与精神分裂症的关联研究

目的 探讨儿茶酚-O-甲基转移酶(catechol-O-methyl transferanse,COMT)基因8个单核苷酸多态性位点(single nRcleotide polymorphism,SNP)与粤东潮汕地区精神分裂症的关系.方法 应用聚合酶链式反应-聚丙烯酰胺凝胶芯片技术检测COMf基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)在粤东潮汕地区的279例精神分裂症患者和100名健康对照中的分布,并借助于plink软件对所得数据进行关联分析.结果 单个位点等位基因频率在两组间的分布差异无统计学意义;单倍型(G)-G-A-A[(rs4680)-rsl65599-rs2075507-rs6269]和单倍型A-A-C-(G)[rs2075507-rs6269-rs4633-(rs6267)]频率两组分布差异有统计学意义,精神分裂症组低于正常对照组,提示它们可能是精神分裂症的保护因素.结论 在中国粤东地区汉族人群中,COMT基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)与精神分裂症无关联性,其中的两个单倍型可能是精神分裂症的保护因素.但本研究不能排除COMT基因可能存在其他功能性变异位点与精神分裂症相关.     

儿茶酚-O-甲基转移酶基因单核苷酸多态性位点与精神分裂症的关联研究

目的 探讨儿茶酚-O-甲基转移酶(catechol-O-methyl transferanse,COMT)基因8个单核苷酸多态性位点(single nRcleotide polymorphism,SNP)与粤东潮汕地区精神分裂症的关系.方法 应用聚合酶链式反应-聚丙烯酰胺凝胶芯片技术检测COMf基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)在粤东潮汕地区的279例精神分裂症患者和100名健康对照中的分布,并借助于plink软件对所得数据进行关联分析.结果 单个位点等位基因频率在两组间的分布差异无统计学意义;单倍型(G)-G-A-A[(rs4680)-rsl65599-rs2075507-rs6269]和单倍型A-A-C-(G)[rs2075507-rs6269-rs4633-(rs6267)]频率两组分布差异有统计学意义,精神分裂症组低于正常对照组,提示它们可能是精神分裂症的保护因素.结论 在中国粤东地区汉族人群中,COMT基因的8个SNP位点(rs4680、rs4818、rsl65599、rs737865、rs2075507、rs6267、rs6269、rs4633)与精神分裂症无关联性,其中的两个单倍型可能是精神分裂症的保护因素.但本研究不能排除COMT基因可能存在其他功能性变异位点与精神分裂症相关.     

儿茶酚-O-甲基转移酶基因Val158Met多态性与催眠感受性的关联研究

目的 探讨儿茶酚-O-甲基转移酶基因(catechol-O-methytransferase,COMT)Val158Met多态性与催眠感受性有无关联.方法 成都市6所高校120名正常汉族大学生参加了实验.按斯坦福团体催眠感受性量表C式(Stanford Group Hypnotic Susceptibility Scale,Form C,SGHSS:C)进行划分,总分0～5分为低催眠感受性组,6～11分为高催眠感受性组.聚合酶链反应-限制性片段长度多态方法检测COMT基因Val158Met多态.结果 在男性样本中,VaL/Val纯合子可能与催眠高感受性关联(VaL/Val vs.Val/Met:0R=5.33,P=0.034;VaL/Val vs.VaL/Met+/Met/Met:OR=4.86,P=0.031).在总样本及女性组中无关联.3种基因型组别样本的催眠感受性差异没有统计学意义.结论 COMT基因val158Met多态可能与男性催眠高感受性父联.该发现有待于增加样本加以证实.     

注意缺陷多动障碍与儿茶酚-O-甲基转移酶基因Val158Met多态性的关联分析

目的探讨注意缺陷多动障碍(attention-deficit hyperactivity disorder,ADHD)汉族患儿与儿茶酚-O-甲基转移酶(catechol-O-methyltransferase,COMT)基因第158位密码子G→A点突变所引起的缬氨酸→甲硫氨酸(Val158Met)的错义突变多态性的关系.方法采用聚合酶链反应-限制性片段长度多态性技术,分析了117例符合DSM-Ⅳ诊断标准的上海汉族ADHD患儿与105例正常健康对照组的COMT基因的Val158Met多态性位点频率.结果 ADHD组的A等位基因频率为25.21%,而对照组为23.81%,两组差异无显著性(χ2=0.5197, P＞0.05). COMT各基因型的分布频率在ADHD和对照组之间的差异也无显著性(P＞0.05).结论汉族儿童注意缺陷多动障碍COMT基因Val158Met多态性可能与ADHD无关联.     

Neuregulin 1基因多态性与中国汉族精神分裂症关联分析

目的 探讨Neuregulin 1(NRG1)基因多态性与精神分裂症的关联.方法 在258个中国汉族精神分裂症核心家系(患者及其亲生父母)中,应用实时定量PCR技术检测位于NRGl基因5'端的4个单核苷酸多态(single nucleotide polymorphism,SNP)位点:rs221533(C/T)、rs7820838(C/T)、433E1006 (A/G)和rs3924999(C/T),进行基因分型,应用传递不平衡检测(transmission disequilibrium test,TDT)分析等位基因传递情况,分析该基因与精神分裂症易感性的关联.结果 在258个中国汉族核心家系中,rs221533、433E1006、rs3924999三个SNP均存在有统计学意义的传递不平衡,优先传递的等位基因分别是:C、A、T(rs221533:X2=27.45,P=0.000;433E1006:X2=56.08,P=0.000;rs3924999:X2=10.53,P=0.001).rs7820838未检到不平衡传递(X2=3.31,P=0.081).频率大于1%单倍型进行分析,rs221533-rs7820838-433E1006联合分析,单倍型C/C/G和C/C/A优先传递(C/C/G:X2=5.26,P=45.08;C/C/A:X2=0.026,P=0.000);rs221533-rs7820838-433E1006-rs3924999联合分析,单倍型C/C/G/T、C/C/A/C和C/C/A/T优势传递(C/C/G/T:X2=10.71,P=0.001;C/C/A/C:.)X2=8.83,P=0.006、C/C/A/T:X2=27.00,P=0.000).213个阳性亚型的精神分裂症核心家系中传递不平衡得出基本一致的结果 .结论 Nrg1基因多态性与中国汉族人群精神分裂症存在关联,尤其是支持与阳性亚型精神分裂症存在关联.     

一个中国汉族精神分裂症高发家系的全基因组连锁分析

目的 对一个汉族精神分裂症高发家系进行全基因组连锁分析,对易感基因进行定位.方法 抽取受试者外周血4 mL,用常规酚氯仿法提取基因组DNA,选择Illumina Infinium Linkage-24 BeadChips芯片对样本进行单核苷酸多态性检测及分型.用Illumina BeadStudio软件处理原始数据后,对分型结果应用Merlin软件进行两点非参数连锁分析和两点参数连锁分析.结果 用Merlin软件进行两点非参数连锁分析,共发现27个连锁值较高的位点(连锁值在0.63～0.75之间,P＜0.05),其中3个单核苷酸多态性(rs993694、rs992690、rs1861577)位于12p12.3区,剩余的位点均位于4p12-q22区.在显性模型下的两点参数连锁分析得到了几乎一致的结果.结论 染色体4p12-q22区以及12p12.3区可能包含精神分裂症的易感基因.     

网状内皮素4受体基因多态性与中国汉族精神分裂症关联分析

目的:分析网状内皮素4受体(RTN4R)基因上的5个单核苷酸多态性(SNP)与中国汉族精神分裂症关联,探讨RTN4R基因单核苷酸多态性与精神分裂症易感性的关系。方法:收集符合美国精神障碍诊断与统计手册第4版(DSM-Ⅳ)诊断的528名偏执型精神分裂症患者,在同一地域招募健康体检者528名作为对照,并采用阳性与阴性症状量表(PANSS)评估234例首次发病患者的临床症状,采用基因分型芯片对RTN4R基因上的5个功能单核苷酸多态性位点进行基因分型,分析多态性与疾病的关联性,以及PANSS因子分与RTN4R多态性的关联。结果:成功检测5个单核苷酸多态性位点的基因型,关联分析显示这些位点基因型和等位基因频率分布病例和对照之间差异无统计学意义。与携带rs696880位点GG基因型患者相比,携带AA基因型患者PANSS阳性分[(23.5±5.6)vs.(25.1±7.6),P0.05]、一般精神病理症状分[(42.6±9.9)vs.(46.0±13.4),P0.05]均较低,携带AA基因型患者发病年龄晚于携带GG型患者[(24.9±8.1)岁vs.(22.2±6.2)岁,P0.05]。结论:在中国汉族人群中,RTN4R基因多态性与精神分裂症可能不存在关联,但可能影响疾病表现。     

Effect of functional catechol-O-methyltransferase Val158Met polymorphism on physical aggression

Genetic and psychological analysis of the relationships between catechol-O-methyltransferase Val158Met polymorphism and various types of aggressiveness was performed in 114 women. Dispersion analysis revealed significant association of ValVal genotype with elevated physical aggression. __________ Translated from Byulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 145, No. 1, pp. 68–70, January, 2008     

白介素13基因多态性与湖北汉族人群哮喘的关系

目的：为了探讨IL-13基因编码区精氨酸(Arg)110谷氨酰胺(Gln)多态性是否与湖北地区汉族人群哮喘及血浆总IgE水平升高相关。方法：采用PCR-RFLP方法，检测湖北地区43名哮喘患儿、45名成人哮喘患者、31名非哮喘儿童和46名体检健康成人的IL-13外显子4Arg110Gln的等位基因频率和基因型频率。用化学发光法测定血浆总IgE。结果：IL-13基因4257应等位基因a在儿童、成人中的频率分别为0．39、0．32。IL-13基因Arg110Gln多态性的GlnGln型与儿童哮喘和血浆总IgE升高相关(P分别为0．030、0．0009)，但与成人哮喘、血浆总IgE水平之间无统计学意义(P分别为0．219、0．174)。结论：研究显示IL-13外显子4Arg110Gln g/a单核苷酸多态性与湖北汉族儿童哮喘和血浆总ISE水平相关，但与成人哮喘、血浆总IgE水平之间无统计学意义。     

Influence of catechol-O-methyltransferase Val158Met polymorphism on neuropsychological and functional outcomes of classical rehabilitation and cognitive remediation in schizophrenia

Neurocognitive deficits are recognized as core features of schizophrenia and have a great impact on functional outcome. Recent reports have suggested that a functional polymorphism, Val158Met, of the catechol-O-methyltransferase (COMT) gene, partially influences cognitive performances (mainly cognitive flexibility and working memory) both in schizophrenic patients and in healthy controls, probably by modulating prefrontal dopamine function. While previous studies focused on single evaluation of cognitive functioning, we aimed to analyse the additive effect of COMT genotype and cognitive exercise on dynamic modulation of cognitive performances. We analysed the COMT Val158Met polymorphism in 50 patients with chronic schizophrenia randomly allocated to two treatment conditions for 3 months: standard rehabilitation treatment (SRT) alone and SRT plus specific cognitive exercise of impaired functions. We then divided our sample in four subgroups on the basis of genotype (Val/Val versus Met carriers) and treatment (placebo versus active). We assessed patients with a neuropsychological battery, the Positive and Negative Symptoms Scale (PANSS) and the Quality of Life Scale (QLS) at enrolment, after 3 months of therapy and after further 3 months of follow-up. We found significantly greater improvement of cognitive flexibility performance and QLS total score for Met carriers on active treatment in comparison to Val/Val on placebo. The findings support the hypothesis that COMT polymorphism influences individual capacity to recover from cognitive deficit through rehabilitation therapy after a wider intervention also including deficit-specific cognitive exercise as a potentiating tool.     

Association analysis of an (AC)n repeat polymorphism in the GABAB receptor gene and schizophrenia

The human γ‐aminobutyric acid type B (GABA_B) receptor gene is a candidate gene for schizophrenia due to its chromosomal location and neurobiologic roles. In the present study, association analyses of genetic polymorphisms of the GABA_B receptor gene with schizophrenia were carried out in 102 unrelated schizophrenic patients and 100 healthy controls, using a polymerase chain reaction‐based, single‐strand conformational polymorphism analysis. Although the Ala20Val and Gly489Ser mutations were not found in our samples, we found a novel polymorphism of (AC)n dinucleotide repeats located approximately 1.6 kb upstream from the translational start site. No significant difference in allele frequencies was found between controls and patients with schizophrenia (P = 0.0587) using the Monte Carlo method. Significant differences were found between controls and patients with continuous‐course schizophrenia (P = 0.0019), and between controls and patients with a positive family history of psychoses (P = 0.0015). These differences, however, were not significant after Bonferroni correction. These data did not support our hypothesis that polymorphisms of the GABA_B receptor gene may confer vulnerability for schizophrenia. © 2002 Wiley‐Liss, Inc.     

OX40基因rs2298212位点与汉族人群冠状动脉粥样硬化疾病的关联研究

目的 探讨OX40基因(TNFRSF4)rs2298212G/A位点与山东汉族人群冠状动脉粥样硬化疾病的相关性.方法 在山东大学齐鲁医院心内科和健康体检中心分别收集到冠状动脉粥样硬化疾病患者536例和正常对照544名,采用聚合酶链反应-限制性片段长度多态性方法 对OX40基因rs2298212G/A多态性位点进行基因分型,并对数据进行统计分析.结果 基因型与等位基因频率分布在病例组与对照组之间差异均无统计学意义(P＞0.05).在回归校正了年龄、性别、体重指数、收缩压、舒张压、血糖、总胆固醇及甘油三酯等因素的影响后,基因型频率分布差异仍无统计学意义(P＞0.05).在对冠状动脉受累支数进行的分层分析发现,受累1支与受累3支之间,基因型与等位基因频率分布差异均有统计学意义(P＜0.05).结论 OX40基因rs2298212G/A多态位点同山东汉族人群冠状动脉粥样硬化疾病之间无关联性存在,但该位点可能与冠状动脉粥样硬化的严重程度相关.     

Relations between catechol-O-methyltransferase Val158Met genotype and inhibitory control development in childhood

The Val158Met rs4680 single-nucleotide polymorphism (SNP) at the catechol-O-methyltransferase (COMT) gene, primarily involved in dopamine breakdown within prefrontal cortex, has shown relations with inhibitory control (IC) in both adults and children. However, little is known about how COMT genotype relates to developmental trajectories of IC throughout childhood. Here, our study explored the effects of the COMT genotype (Val/Val, Val/Met, and Met/Met) on IC trajectories between the ages of 5 and 10 years. Children (n = 222) completed a Go/Nogo task at ages 5, 7, and 10; IC was characterized using signal detection theory to examine IC performance (d′) and response strategy (RS) (criterion). COMT genotype was not related to initial levels of IC performance and RS at age 5 or change in RS from ages 5 to 10. In contrast, COMT genotype was related to change in IC performance between 5 and 10 years. While Val/Val children did not differ from Val/Met children in development of IC performance, children with the Met/Met genotype exhibited more rapid development of IC performance when compared with Val/Met peers. These results suggest that COMT genotype modulates the development of IC performance in middle childhood.