中国辽宁锡伯族群体3个短串联重复位点的遗传多态性分析

背景：对常染色体STR基因座的多态性的研究可为法医学亲权鉴定提供基础数据。 目的：探索辽宁锡伯族D16S539,THO1,D13S317 3个常染色体基因座的遗传多态性,建立锡伯族群体的遗传学基础数据。 方法：采集辽宁省沈阳市新城子区黄家乡锡伯族中小学的150名中小学生口腔黏膜细胞,Chelex 100法提取DNA,进行荧光标记PCR扩增,产物在Li-COR 4300基因分析仪上进行电泳,E-seq分析软件计算扩增产物片段相对大小,进行基因型分型。调查辽宁地区锡伯族群体 3个 STR基因座等位基因频率,进行遗传多态性分析。 结果与结论：辽宁锡伯族群体中3个STR基因座具有遗传多态性,其基因型分布符合Hardy-Weinberg平衡定律。辽宁锡伯族群体中3个STR基因座的杂合度分布在0.769~0.810;个人识别力分布在0.824~0.929,累积个人识别能力为0.999;多态信息量分布在 0.650~0.790;非父排除率分布在0.565~0.790,累积非父排除率为0.979。说明辽宁锡伯族群体3个常染色体STR基因座有较高的非父排除率和个体识别能力,可为法医学亲子鉴定和个体识别及移植配型等遗传学研究提供依据。     

双相情感障碍患者冲动攻击行为与5-HTR1B 基因的关联性研究

目的 探讨维吾尔族及汉族双相情感障碍（BPD）患者的冲动攻击行为与5-HTR1B rs6296 基因多态性的关联性。方法 采用病例-对照的研究方法共收集868 例BPD 抑郁发作期患者，根据民 族和有无冲动攻击行为分为4组：维吾尔族BPD 患者有冲动攻击行为组184例（男性92例、女性92 例）、无 冲动攻击行为组326 例（男性174 例、女性152 例），汉族BPD 患者有冲动攻击行为组112 例（男性50 例、 女性62 例）、无冲动攻击行为组246 例（男性134 例、女性112 例）。采用修改版外显行为攻击量表（MOAS） 对入组患者评估。通过PCR直接测序法对rs6296基因多态性进行鉴定。结果 汉族BPD患者有冲动攻 击行为组与无冲动攻击行为组5-HTR1B rs6296 位点的基因型及等位基因频率分布差异均无统计学意义 （P＞ 0.05）；维吾尔族有冲动攻击行为组与无冲动攻击行为组5-HTR1B rs6296 位点基因型及等位基因频 率分布差异均有统计学意义（P ＜ 0.05）。结论 汉族BPD患者冲动攻击行为与5-HTR1B rs6296 基因多 态性无相关性。维吾尔族BPD 患者冲动攻击行为与5-HTR1B rs6296 基因多态性有相关性。等位基因G 可能增加维吾尔族BPD 患者的冲动攻击行为的风险。     

D6S1043、D12S391基因座与主动攻击行为的关联研究

目的:探讨D6S1043、D12S391基因座的基因多态性对主动攻击行为的影响。方法:应用聚合酶链反应技术结合毛细管电泳法对114例男性主动攻击行为者(研究组)及120名健康男性(对照组)进行D6S1043、D12S391基因座的基因型及等位基因检测,分析D6S1043、D12S391基因座多态性与主动攻击行为的相关性。结果:研究组D6S1043基因座中12~19基因型频率(13.16%)明显高于对照组(1.67%)(P0.05);两组等位基因频率差异无统计学意义;两组D12S391基因座的基因型及等位基因频率差异无统计学意义。结论:D6S1043基因座中12~19基因型可能主动攻击行为有关。     

中国南方汉人D13S316位点多态性及Wilson病基因诊断的研究

目的　评估中国南方汉人Wilson病 (WD)基因 (WND)侧翼微卫星DNA(STR)位点D13S3 16的基因多态性及在WD基因诊断中的价值。方法　采用聚合酶链反应 (PCR)、变性聚丙烯酰胺凝胶电脉和银染法分析 84名无血缘关系中国南方汉人D13S3 16的片段长度多态性 ;并对 19个WD家系进行STR连锁分析。结果　D13S3 16有 19个等位片段 ,长度范围为 13 4～ 170bp ,多态信息含量 (PIC)为 0 93 1。共检出 8例症状前患者 ,10例致病基因携带者及 15例正常人 ,3例未能确定 ,基因诊断率达 91 67%。结论　D13S3 16大致代表中国南方汉人的多态性标记 ,对WD基因诊断有重要价值。     

酒依赖共病双相情感障碍患者冲动攻击行为与5-HTR1B基因多态性关联分析

目的探讨酒依赖共病双相情感障碍患者的冲动攻击行为与5-HTR1B rs6296基因多态性的关联,为酒依赖共病双相情感障碍患者冲动攻击行为导致病理生理改变机制的潜在遗传学差异的研究提供参考。方法采用病例对照研究,纳入符合《精神障碍诊断与统计手册(第4版)》(DSM-IV)酒依赖共病双相情感障碍诊断标准的患者230例,依据修订版外显攻击行为量表(MOAS)评分分为有冲动攻击行为组(n=128)和无冲动攻击性行为组(n=102)。通过PCR直接测序法对rs6296基因多态性进行测定,并分析5-HTR1B rs6296基因多态性与酒依赖共病双相情感障碍患者冲动攻击行为的关联性。结果酒依赖共病双相情感障碍患者有冲动攻击行为组与无冲动攻击行为组rs6296位点的等位基因频率分布差异无统计学意义(χ~2=2.135,P0.05);两组rs6296位点基因型分布差异无统计学意义(χ~2=2.771,P0.05)。结论酒依赖共病双相情感障碍患者冲动攻击行为与5-HTR1B rs6296基因多态性无关联。     

同胞精神分裂症患者与染色体D6S274和D6S296位点的关联分析

目的　探讨精神分裂症与6号染色体上基因位点多态性之间的关系。方法　选取南京市及其周边地区共患慢性精神分裂症的同胞60对(120例)及散发性精神分裂症120例,分别与正常同胞60对(120名)及120名正常人进行对照。采用聚合酶链反应限制性片段长度多态性技术,观察其D6S274和D6S296位点多态性的分布。结果　精神分裂症患者和正常人D6S274和D6S296位点上等位基因频率的分布均符合Hardy Weinberg平衡。共患慢性精神分裂症同胞组D6S296的264bp和278bp等位基因频率分别为20 83%和21 67%,高于正常同胞组(分别为7 08%和14 17% ),差异均有统计学意义(χ2 =18 84和4 59,P<0 01和P<0 05);其他各等位基因频率的分布在各组之间的差异无统计学意义。结论　慢性精神分裂症可能与人类6号染色体上D6S296位点关联。     

5-羟色胺1Dβ受体基因861G／C多态性与强迫症关联的病例对照研究

目的：探讨5-羟色胺lDr3受体（5-HTRlDβ）基因861G／C多态性与强迫症的关联性。方法：对239例强迫症（强迫症组）患者和337名健康对照（对照组）通过聚合酶链式反应与限制性片段长度多态性基因分型技术对5-HTRlDB基因单核苷酸多态性位点861G／C进行基因分型。结果：861G／C位点基因型频率分布两组问比较差异有统计学意义（X2=7．59,df=2,P=0．023）,而等位基因频率分布差异无统计学意义;杂合子GC基因型与纯合子（GG＋CC）基因型（X。=4．59,P=0．03,OR=1．44,95％CI：1．03～2．01）或CC基因型与GG＋GC基因型（X2=6．85,P=0．009,OR：0．58,95％C1=0．38～0．87）两组间比较差异有统计学意义,而GG基因型与GC＋CC基因型差异无统计学意义。两组女性之间比较,基因型（）f。=11．98,df=2,P：0．0025）与等位基L天J频率（X。=4．90,af=1,P=0．03,OR=1．51,95％C1=1．05～2．17）分布差异有统计学意义,而两组男性之间比较,基因型与等位基因频率分布差异无统计学意义。,强迫症晚发（〉16岁）组与对照组基因型频率分布差异有统计学意义（×。=6．45,妙=2,P=0．04）,而等位基因频率分布差异无统计学意义;强迫症早发（≤16岁）组、强迫症临床3个亚组基因型与等位基因频率分布上与对照组之间差异均无统计学意义。结论：5-HTR1Dβ861G／C多态性可能与强迫症和晚发型强迫症仔在关联;G等位基因可能是女性强迫症的风险因子。     

短串联重复序列基因座与冲动暴力行为的关联研究

目的 探讨冲动暴力行为与相关短串联重复序列基因座的关联情况.方法 运用AmpFISTR IdentifilerTM荧光标记复合扩增体系,对203例冲动暴力行为罪犯(研究组)与207名非暴力行为健康个体(对照组)样本进行聚合酶链反应复合扩增,然后应用ABI3100型基因分析系统对扩增产物进行电泳和基因检测,观察2组15个STR基因座等位基因及基因型频率的差异.结果 15个STR基因座均符合遗传平衡定律(Hardy-Weinberg定律)；研究组与对照组THO1和TPOX基因座的等位基因频率分布的差异有统计学意义(P＜0.05)；研究组和对照组THO1-10频率分别为0.0172和0.0580,差异有统计学意义(P=0.002,OR=0.29,95％ CI:0.12 ～0.67)；研究组和对照组TPOX-11频率分别为0.3621和0.2391,差异有统计学意义(P=0.000,OR=1.81,95％ CI:1.33 ～ 2.45)；其他STR基因座等位基因频率及所有基因型频率2组差异均无统计学意义(P＞0.05).结论 THO1和TPOX基因座多态性与冲动暴力行为可能存在关联,等位基因THO1-10、TPOX-11与冲动暴力行为的发生可能有一定关系.     

中国人D13S296位点多态性检测及肝豆状核变性的基因诊断

目的评估中国人群肝豆状核变性(HLD)基因(WND)侧翼短重复序列(STR)位点D13S296的基因多态性及其临床应用价值.方法采用聚合酶链反应(PCR)、变性聚丙烯酰胺凝胶电泳和银染法分析98名无血缘关系中国人D13S296的片段长度多态性;并对19个HLD家系进行STR多态性分析.结果D13S296有18个等位片段,长度范围为106～140bp,多态信息含量(PIC)为0.906.共检出8例症状前患者,10例基因携带者及14例正常人,4例未能确定.基因诊断率达88.87%.结论D13S296在中国人群是较优秀的多态性标记,对HLD基因诊断有较重要的临床应用价值.     

江苏地区15个STR基因座遗传多态性与自杀行为的关联研究

目的 通过对15个STR基因座遗传多态性的分析,了解自杀行为与STR基因座相关等位基因的关联情况.方法 运用AmpFISTR IdentifilerTM荧光标记复合扩增体系对76名自杀者与147名随机个体进行PCR复合扩增,然后应用AB13100型基因分析系统对扩增产物进行电泳和基因检测.观察两个群体中15个STR基因座等位基因频率的差异.结果 15个STR基因座均符合Hardy-Weinberg平衡;CSF1PO-13(自杀组:10.53%,对照组:5.10%)、D13S317-8(自杀组:38.82%,对照组:27.89%)、FGA-18(自杀组:2.63%,对照组:0.34%)、FGA-19(自杀组:7.89%,对照组:3.06%)、FGA-23(自杀组:17.11%,对照组:27.89%)、vWA-16(自杀组:9.31%,对照组:18.37%)、D2S1338-22(自杀组:0.66%,对照组:5.10%)、D16S539-9(自杀组:25.66%,对照组:35.71%)在两组人群中的等位基因频率存在显著差异(P<0.05);D2S1338-25(自杀组:16.45%,对照组:5.44%)在两组人群中的等位基因频率存在极显著差异(P<0.01).其余STR基因座在两个群体中的等位基因频率均无显著差异(P>0.05).结论 等位基因CSF1PO-13、D13S317-8、FGA-18、FGA-19、FGA-23、D2S1338-22、D2S1338-25、vWA-16、D16S539-9可能与自杀行为的发生有一定关系,在2号、4号、5号、12号、13号和16号染色体上可能存在与自杀行为相关的基因.     

Suicide attempts and the tryptophan hydroxylase gene

Tryptophan hydroxylase (TPH) is the rate-limiting enzyme of serotonin synthesis. In this case-control study, we investigated whether the TPH gene was a susceptibility factor for suicidal behavior. Seven polymorphisms spanning the entire gene were studied in a case-control study including 231 individuals who had attempted suicide and 281 controls. Significant associations were found between variants in introns 7, 8 and 9 (chi(2) = 11.2, df = 1, P< 0.0008 for the allele distribution; these loci are in complete linkage disequilibrium) and in the 3' noncoding region (chi(2) = 30.94, P = 0.0014) and suicide attempt. The association was strongest for subjects who had attempted suicide by violent means and who had a history of major depression. No significant association was observed between suicide attempts and polymorphisms in the promoter, intron 1 and intron 3. The results presented here, and those of previous studies, suggest that a genetic variant of the 3' part of the TPH gene may be a susceptibility factor for a phenotype combining suicidal behavior, mood disorder and impulsive aggression.     

Cholesterol concentrations in violent and non-violent women suicide attempters.

The aim of this study was to evaluate whether women with a history of violent suicide attempts have lower serum cholesterol concentrations than those who attempted suicide by non-violent methods. Our retrospective study used a case-control design to compare serum total cholesterol concentration, hematocrit, red blood cell count and body mass index (BMI) in women with a history of violent (n = 19) or non-violent (n = 51) suicide attempts and of non-suicidal controls (n = 70) matched by diagnosis and age. Analysis of covariance (ANCOVA) with age as the covariate was used to analyze differences in cholesterol levels in groups according to violence. Violence was found to be a significant factor (P = 0.016). Using the Scheffé test, a significant difference (P = 0.011) was revealed between the group of violent and non-violent suicide attempters and between the violent suicide attempters and the control group. Patients with a violent suicidal attempt have significantly lower cholesterol levels than patients with non-violent attempts and the control subjects. Our findings suggest that suicide attempts should not be considered a homogeneous group. They are consistent with the theory that low levels of cholesterol are associated with increased tendency for impulsive behavior and aggression and contribute to a more violent pattern of suicidal behavior.     

Association between violent suicidal behavior and the low activity allele of the serotonin transporter gene

There is compelling evidence that serotonin system dysfunction is associated with certain behavioral disorders, such as suicidal behavior and impulsive aggression. A functional polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR) was recently identified and the presence of the short allele found to be associated with a lower level of expression of the gene, lower levels of 5-HT uptake, suicidal behavior and anxiety-related traits. We genotyped 51 West European Caucasians who had made violent suicide attempts and 139 controls of the same ethnic origin, with no history of suicidal behavior. The frequencies of the S allele and the SS genotype were significantly higher in the violent suicide attempters than in the controls. The odds ratio for the SS genotype vs the LL genotype was 3.63 (95% CI (1.27--10.40)). This suggests that a change in expression of the gene encoding the 5-HT transporter may be involved in violent suicidal behavior.     

The interacting role of media violence exposure and aggressive-disruptive behavior in adolescent brain activation during an emotional Stroop task

Only recently have investigations of the relationship between media violence exposure (MVE) and aggressive behavior focused on brain functioning. In this study, we examined the relationship between brain activation and history of media violence exposure in adolescents, using functional magnetic resonance imaging (fMRI). Samples of adolescents with no psychiatric diagnosis or with disruptive behavior disorder (DBD) with aggression were compared to investigate whether the association of MVE history and brain activation is moderated by aggressive behavior/personality. Twenty-two adolescents with a history of aggressive behavior and diagnosis of either conduct disorder or oppositional-defiant disorder (DBD sample) and 22 controls completed an emotional Stroop task during fMRI. Primary imaging results indicated that controls with a history of low MVE demonstrated greater activity in the right inferior frontal gyrus and rostral anterior cingulate during the violent word condition. In contrast, in adolescents with DBD, those with high MVE exhibited decreased activation in the right amygdala, compared with those with low MVE. These findings are consistent with research demonstrating the importance of fronto-limbic structures for processing emotional stimuli, and with research suggesting that media violence may affect individuals in different ways depending on the presence of aggressive traits.     

Relationships between attempted suicide, temperamental vulnerability, and violent criminality in a Swedish forensic psychiatric population.

The relationship between suicide attempts and different vulnerability factors was investigated in 61 male subjects during forensic psychiatric examination. Personality traits and psychopathy were determined by means of the Karolinska Scales of Personality (KSP) and the Psychopathy Checklist-Revised (PCL-R). Clinical diagnoses were determined by the use of Structured Clinical Interview for DSM-III-R (SCID). Platelet monoamine oxidase (MAO) activity was investigated in 58 subjects.Suicide attempters had extremely low socialization and high impulsive aggression. This was independent of a history of repeatedly criminal violence or not. They had higher PCL-R scores and lower levels of platelet MAO activity than non-attempters. No relationship was found between suicide attempts and repeated violent criminality. However, among the subjects with repeated criminal violence there was a highly significant difference between suicide attempters and non-attempters, indicating different personality profiles in violent offenders with and without suicidal behavior. Suicidal behavior was significantly associated with borderline personality disorder, but not with any other single DSM-III-R disorder. The results show a far more severe personality disturbance in suicide attempters than in other violent patients in this type of population. Suicidal behavior should therefore be evaluated and treated per se.     

Sleep architecture in homicidal women with antisocial personality disorder--a preliminary study

The aim of the present study was to characterize sleep in severely violent women with antisocial personality disorder (ASP) as the primary diagnosis. Participants for this preliminary study were three drug-free female offenders ordered to undergo a forensic mental examination in a maximum security state mental hospital after committing homicide or attempted homicide. Ten healthy age- and gender-matched controls consisted of hospital staff with no history of physical violence. The most striking finding was the increased amount of slow wave sleep, particularly the deepest sleep stage, S4, in women with ASP. This finding is in agreement with previously reported results in habitually violent male criminals with ASP. Severe female aggression seems to be associated with profound changes in sleep architecture. Whether this reflects specific brain pathology, or a delay in the normal development of sleep patterns in the course of aging, needs to be clarified. From the perspective of sleep research, the biological correlates of severe impulsive violence seem to be similar in both sexes.     

BDNF基因多态性与男性青少年暴力攻击行为的关联性分析

目的 分析BDNF基因与青少年男性暴力行为之间的关系.方法 采用TaqMan探针SNP基因分型技术对139例男性暴力少教人员,98例非暴力男性少教人员以及259例正常成年男性进行BDNF基因(rs1103010,rs6265)位点的基因分型.分析攻击组和对照组的等位基因和基因型分布规律.结果 器力青少年男性rs1103010位点T等位基因频率高于正常对照组(31.7%vs 24.9%,P＜0.05),rs1103010与rs6265两位点构成的T-G单体型在暴力组中的频率也显著高于正常对照组(31.4%VS 23.4%.P＜0.05).结论 BDNF基因可能在青少年暴力行为的发生中起了作用.     

Dopamine D3 receptor gene polymorphism and violent behavior: relation to impulsiveness and ADHD-related psychopathology

Summary. Several lines of evidence indicate that dopaminergic neurotransmission is involved in the regulation of impulsive aggression and violence and that genetically determined variability in dopaminergic gene expression modifies complex traits including that of impulsivity and aggression. In this study we report an association of the dopamine D3 receptor (DRD3) polymorphism with impulsiveness according to Eysenck's EIQ and scores on the German short version of the Wender Utah Rating Scale (WURS-k), which we used for the assessment of a history of ADHD-related symptoms. This association was detected in a group of violent offenders, but not in non-violent individuals. Highest scores of EIQ impulsiveness and of the WURS-k were found in heterozygous violent individuals, while homozygotes showed significant lower rating scores, suggesting an heterosis effect. The results of our study suggest that variations of the DRD3 gene are likely involved in the regulation of impulsivity and some psychopathological aspects of ADHD related to violent behavior. Received August 7, 2002; accepted December 4, 2002 Published online February 19, 2003 Authors' address: Dr. W. Retz, Institute for Forensic Psychology and Psychiatry, University of the Saarland, D-66421 Homburg/Saar, Federal Republic of Germany, e-mail: wolfgang.retz@uniklinik-saarland.de     

Monitoring and predicting the risk of violence in residential facilities. No difference between patients with history or with no history of violence

BackgroundMost people with mental disorders are not violent. However, the lack of specific studies in this area and recent radical changes in Italy, including the closure of six Forensic Mental Hospitals, has prompted a more detailed investigation of patients with aggressive behaviour.AimsTo compare socio-demographic, clinical and treatment-related characteristics of long-term inpatients with a lifetime history of serious violence with controls; to identify predictors of verbal and physical aggressive behaviour during 1-year follow-up.MethodsIn a prospective cohort study, patients living in Residential Facilities (RFs) with a lifetime history of serious violence were assessed with a large set of standardized instruments and compared to patients with no violent history. Patients were evaluated bi-monthly with MOAS in order to monitor any aggressive behaviour.ResultsThe sample included 139 inpatients, 82 violent and 57 control subjects; most patients were male. The bi-monthly monitoring during the 1-year follow-up did not show any statistically significant differences in aggressive behaviour rates between the two groups. The subscale explaining most of the MOAS total score was aggression against objects, although verbal aggression was the most common pattern. Furthermore, verbal aggression was significantly associated with aggression against objects and physical aggression.ConclusionsPatients with a history of violence in RFs, where treatment and clinical supervision are available, do not show higher rates of aggressiveness compared to patients with no lifetime history of violence. Since verbal aggression is associated with more severe forms of aggression, prompt intervention is warranted to reduce the risk of escalation.     

Association of low-activity MAOA allelic variants with violent crime in incarcerated offenders

The main enzyme for serotonin degradation, monoamine oxidase (MAO) A, has recently emerged as a key biological factor in the predisposition to impulsive aggression. Male carriers of low-activity variants of the main functional polymorphism of the MAOA gene (MAOA-uVNTR) have been shown to exhibit a greater proclivity to engage in violent acts. Thus, we hypothesized that low-activity MAOA-uVNTR alleles may be associated with a higher risk for criminal violence among male offenders. To test this possibility, we analyzed the MAOA-uVNTR variants of violent (n = 49) and non-violent (n = 40) male Caucasian and African-American convicts in a correctional facility. All participants were also tested with the Childhood Trauma Questionnaire (CTQ), Barratt Impulsivity Scale (BIS-11) and Buss-Perry Aggression Questionnaire (BPAQ) to assess their levels of childhood trauma exposure, impulsivity and aggression, respectively. Our results revealed a robust (P < 0.0001) association between low-activity MAOA-uVNTR alleles and violent crime. This association was replicated in the group of Caucasian violent offenders (P < 0.01), but reached only a marginal trend (P = 0.08) in their African American counterparts. While violent crime charges were not associated with CTQ, BIS-11 and BPAQ scores, carriers of low-activity alleles exhibited a mild, yet significant (P < 0.05) increase in BIS-11 total and attentional-impulsiveness scores. In summary, these findings support the role of MAOA gene as a prominent genetic determinant for criminal violence. Further studies are required to confirm these results in larger samples of inmates and evaluate potential interactions between MAOA alleles and environmental vulnerability factors.