5-羟色胺转运体基因多态性与青少年抑郁症的关联研究

目的 探讨中国汉族青少年抑郁症与5-羟色胺转运体（5-HTY）基因的启动子区多态（5-HTTLPR）之间的关系。方法 应用聚合酶链式反应（PCR）扩增技术对84例青少年抑郁症患者和85例健康者进行基因型分析。结果 5-HTYLPR基因的3种基因型S／S,L／S和L/L在青少年抑郁症组的分布分别为57．1％,36．9％,6．0％;在对照组分别为57．6％,34．1％,8．2％,两组间差异无显著性（P〉0．05）。抑郁症组中S／S基因型患者HAMD自杀因子评分明显高于L／L和L／S型患者（P〈0.01）。结论 5-HTT基因多态性与青少年抑郁症无明显关联。抑郁症中携带S／S基因型患者的自杀风险相对比L／L型、L／S型患者高。     

5-羟色胺转运体基因多态性与自杀未遂的关联研究

目的探讨5-羟色胺转运体(5-HTT)基因启动子区多态性(5-HTTLPR)与自杀未遂的关系。方法运用聚合酶链反应技术(PCR)检测71例自杀未遂患者和80名健康对照5-HTTLPR基因型。结果自杀未遂组与对照组5-HTTLPR的基因型及等位基因(S/L)频率差异无统计学意义(P>0.05);进一步分析显示,有精神疾病自杀未遂组(37例)的短重复序列S等位基因频率为85.1%,与正常对照组(72.5%)及无精神疾病自杀未遂组(69.1%)的差异均具有统计学意义(X2=4.49,P=0.04;X2=5.21,P=0.03)。结论5-HTTLPR的S等位基因和精神病自杀未遂存在关联。     

5-羟色胺转运体启动子基因多态与青少年抑郁症患者人格特质的关联研究

目的 探讨5-羟色胺转运体启动子基因多态(5-HTTLPR)与青少年抑郁症患者人格特质的关联性.方法 应用聚合酶链式反应(PCR)扩增技术对75例青少年抑郁症患者进行基因型分析,并对其进行艾森克人格问卷(EPQ)儿童版(＜16岁)和成人版(≥16岁)以及自我接纳问卷(sAQ)的测评.结果 携带L等位基因者(I/L和L/S基因型,n=30)EPQ内外向因子分高于不携带L者(S/S基因型,n=44),差异有统计学意义(t=2.68,P=0.009).携带L等位基因的患者(n=31)SAQ自我评价因子分高于不携带L者(n=44),差异有统计学意义(t=2.12,P=0.038).结论 5-HTTLPR多态与青少年抑郁症患者的人格特质存在关联.     

5-羟色胺转运体基因多态性与脑卒中后抑郁的关系

目的 探讨5-羟色胺转运体基因启动子区域多态性(5-HTTLPR)与中国汉族人群脑卒中后抑郁(PSD)的关系.方法 应用PCR技术,比较96例PSD、97例脑卒中后非PSD及60名健康对照组上述位点基因型及等位基因频率.结果 PSD组5-HTTLPR多态的S/S基因型频率和S等位基因频率显著高于脑卒中非PSD组和健康对照组(均P＜0.05),S等位基因与PSD呈正关联(比值比OR=1.76,P＜0.01,95％CI:1.15～2.69).结论 5-HTTLPR S/S基因型和S等位基因可能为脑卒中后抑郁的易患因素.     

5-羟色胺转运体基因多态性与氟西汀疗效及副反应的关系

目的探讨重性抑郁障碍(MDD)氟西汀疗效及不良反应与5-羟色胺转运体启动子区基因多态性(5-HTTLPR)的关系。方法选取符合美国精神障碍诊断与统计手册第4版(DSM-IV)重性抑郁障碍诊断标准的89例患者为研究对象。给予氟西汀治疗6周。利用聚合酶链反应(PCR)多态性技术检测5-HTTLPR多态性。结果不同基因型患者组之间治疗后HAMD总分减分率的差异有统计学意义(P<0.005),L/L基因型组的减分率高于另两种基因型组;有效组和无效组之间、有无恶心不良反应组之间的5-HTTL-PR的基因型和等位基因频率的差异均有统计学意义(P<0.05),L/L基因型组的疗效和恶心发生率高于另2组。结论5-HTTLPR基因多态性可能与氟西汀抗抑郁疗效及其恶心不良反应相关。     

5-羟色胺转运体启动子区基因多态性与强迫症的关联分析

目的:探索汉族人群中的5-羟色胺转运体启动子区(5-HTTLPR)基因多态性与强迫症的发病关系.方法:对强迫症患者(强迫症组)和正常对照者(对照组)分别采用聚合酶链反应扩增片断长度多态技术测定基因型.结果:强迫症组与对照组5-HTTLPR的基因型频率无显著性差异;两组的等位基因频率有显著性差异.L等位基因与强迫症呈正关联(OR=1.929,P＜0.05).结论:5-HTTLPR基因多态性的L等位基因与强迫症相关联,是强迫症的危险因子.     

5-羟色胺转运体启动子区域基因多态性位点与双相障碍的关联研究

目的:探讨5-羟色胺转运体蛋白基因启动子区域(5-HTTLPR)位点多态性与双相障碍之间的遗传学联系。方法:以中国西北地区汉族人群中51例双相障碍患者(患者组)的核心家系(父母组102名)共153人为研究对象;取每个成员血液样本DNA,应用聚合酶链反应技术扩增5-HTTLPR位点,以琼脂糖凝胶电泳法进行基因分型,对5-HTTLPR位点多态性与双相障碍之间分子遗传学联系进行以家系为基础的连锁不平衡分析。结果:无论5-HTTLPR位点各种基因型(L/L、L/LG、S/L、S/S、S/LG)还是等位基因(L、LG、S)频率在患者组和父母组比较差异无统计学意义(χ2=3.732,P0.05;χ2=0.633,P0.05)。基于基因型的单倍体相对风险分析(GHRR)以及传递不平衡分析(TDT)也未发现5-HTTLPR与双相障碍存在连锁不平衡(GHRR:P0.05;TDT:χ2=2.418,P0.05)。结论:5-HTTLPR多态性位点在中国西北地区汉族人群双相障碍发病机制中不起主要作用,但不能排除微效作用的存在。     

5-羟色胺转运体基因多态性与精神分裂症的相关性研究

目的：探讨中国汉族人群中5一羟色胺转运体（5-HTT）基因与精神分裂症之间的相关性。方法：189例符合中国精神障碍分类与诊断标准第3版及美国精神障碍诊断与统计手册第4版精神分裂症诊断标准的患者（患者组）使用聚合酶链式反应扩增5-HTT基因的启动子区（5-HTrLPR）位点和内含子区（5-HTTVNTR）位点,以琼脂糖凝胶电泳分离法进行基因分型,并和300名正常人（正常对照组）进行对照。结果：患者组与正常对照组之间5-HTTLPR位点L／L、L／S和S／S基因型频率以及等位基因L、s频率分布上差异具有统计学意义（x2=47．882,x2=44．188;P〈0．01或P〈0．001）;5-HTTVNTR位点12／12、12／10、10／10基因型频率和等位基因10、12频率分布上差异无统计学意义（X2=0．335,X。=0．051;P均〉0．05）。结论：S／S基因型及S等位基因可能是精神分裂症患者的易感等位基因;5-HT．TVNTR位点在中国汉族人群精神分裂症发病机制中可能不起主要作用。     

5-羟色胺转运体基因启动子区与心境障碍的关联分析

目的 探讨5-羟色胺转运体基因启动子区5-HTTLPR与心境障碍之间的分子遗传学联系。方法 在中国汉族人群中，以心境障碍核心家系作为研究对象，根据哈佛大学提供的遗传学研究用诊断性检查表(DIGS)自编家系调查表，采用DSM-Ⅳ诊断标准并结合一些心理测评工具，以达到表型一致。在72个情感性精神障碍核心家系，222个家系成员(其中双相障碍56例，重性抑郁症34例)中，应用聚合酶链反应(PCR)和限制性片段长度多态性方法，对5-HTT基因启动子区5-HTTLPR与心境障碍之间的分子遗传学联系进行了以家系为基础的连锁不平衡分析结果基因型和等位基因频率在心境障碍患病组和父母对照组之间无显著差异。GHRR和HHRR分析以及多等位基因ETDT统计分析也没有发现存在连锁不平衡。5-HTTLPR位点除了“L”和“S”片段外，还发现2例出现“L^*”(528^*bp)片段，频率约占1％。结论 5-HTYLPR在心境障碍的发病中可能不起重要作用。     

广泛性焦虑障碍与5-羟色胺转运体基因多态性的相关研究

目的　探讨广泛性焦虑障碍与 5 羟色胺转运体 (5 HTT)基因启动子区和内含子 2区两种多态性的相关性。方法　运用聚合酶链反应技术检测 4 7例广泛性焦虑障碍患者 (患者组 )和 90名健康对照者 (对照组 )两种基因多态性的分布频率。结果　患者组启动子区多态性 (5 HTTLPR)的short/short(SS)基因型和short(S)等位基因频率分别为 72 %和 83% ,对照组SS基因型和S等位基因频率分别为 4 9%和 71% ,两组间的差异有显著性 (P <0 0 5 )。内含子 2区数目可变的顺向重复多态性各基因型 (12 / 12 ,12 / 10 ,10 / 10 )频率在患者组中分别为 72 % ,2 6 % ,2 % ,在对照组中分别为 78% ,2 1% ,1% ,两组间的差异无显著性 (P >0 0 5 ) ;等位基因频率比较的差异亦无显著性 (P >0 0 5 )。结论　 5 HTTLPR的SS基因型可能是广泛性焦虑障碍的易感基因之一。     

A polymorphism (5-HTTLPR) in the serotonin transporter promoter gene is associated with DSM-IV depression subtypes in seasonal affective disorder

Serotonergic mechanisms are thought to play an important role in the pathogenesis of seasonal affective disorder (SAD). The expression of the serotonin transporter (5-HTT) is regulated in part by an insertion/deletion polymorphism in the serotonin transporter gene promoter region (5-HTTLPR). The 5-HTTLPR short allele (s) has been associated with anxiety-related personality traits and depression, and one study observed an association between the 5-HTTLPR s-allele and SAD and the trait of seasonality. We genotyped 138 SAD patients and 146 healthy volunteers with low seasonality for 5-HTTLPR. No difference between patients and controls was found for genotype distribution and s-allele frequency. However, genotype distribution and allele frequencies were strongly associated with DSM-IV depression subtypes. Melancholic depression was associated with the 5-HTTLPR long (l) allele and atypical depression with the 5-HTTLPR s-allele (two-sided Fisher's exact test: genotype distribution: P=0.0038; allele frequencies: P=0.007). Our data are compatible with the hypothesis of a disease process that is not causally related to 5-HTTLPR, but involves 5-HT neurotransmission and 5-HTTLPR somewhere on its way to phenotypic disease expression.     

Novel 5-HTTLPR allele associates with higher serotonin transporter binding in putamen: a [(11)C] DASB positron emission tomography study.

BACKGROUND: The serotonin transporter (5-HTT)-linked polymorphic region (5-HTTLPR) has two frequent alleles, designated long (L), and short (S). The S allele is associated with lower levels of 5-HTT mRNA and lower 5-HTT expression in human cell lines. A functional single nucleotide variant was detected within L, designated L(A) and L(G). Only L(A) is associated with high levels of in vitro 5-HTT expression, whereas L(G) is low expressing and more similar to S. We examined the possible influence of the long (A/G) variant on 5-HTT density in the living human brain using 3-(11)C-amino-4-(2-dimethylaminomethylphenyl-sulfanyl) benzonitrile ([(11)C]DASB) positron emission tomography. METHODS: The 5-HTT binding potential (5-HTT BP), an index of 5-HTT density, was found in 43 healthy subjects genotyped for 5-HTTLPR long (A/G), and in an ethnically homogenous subsample of 30 Caucasian-Canadians. RESULTS: The L(A)/L(A) was associated with higher 5-HTT BP in putamen (p = .026, not corrected). This association became stronger in the Caucasian subsample (p = .004) and was significant even after correcting for multiple comparisons. CONCLUSIONS: The 5-HTTLPR long (A/G) polymorphism influences 5-HTT density leading to higher putamen 5-HTT BP in healthy L(A)/L(A) carriers of Caucasian ancestry. This finding extends the role of this polymorphism from in vitro reports of higher 5-HTT expression with the L(A)/L(A) genotype into in vivo brains of healthy human subjects.     

中国汉族人群5-羟色胺转运体基因多态性与神经性厌食的关联研究

目的:探讨中国汉族人群5-羟色胺转运体基因启动子区域(5-HTTLPR)多态性与神经性厌食的关系。方法:应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对198例神经性厌食患者和225例正常健康对照者进行基因分型和关联分析。结果:①5-HTTLPR基因的3种基因型S/S、L/S和L/L在神经性厌食组的分布频率分别为65.7%、26.8%、7.6%,对照组为48.8%、37.8%、13.4%,两组差异有统计学意义(P<0.05)。等位基因S、L在神经性厌食组的分布分别为79.0%、21.0%,对照组为69.3%、30.7%,差异有统计学意义(P<0.05)。患病与携带L等位基因成负关联(OR=0.52,95%CI:0.35～0.77),患病与L/S基因型成负关联(OR=0.52,95%CI:0.34～0.79)。②5-HTTLPR功能三等位基因型(LA/LA、S/LA+LA/LG、S/S+S/LG+LG/LG)在神经性厌食组分布频率分别为2.0%、12.2%、85.8%,对照组为4.1%、23.4%、72.5%,两组差异有统计学意义(P<0.05)。患病与携带LA等位基因成负关联(OR=0.44,95%CI:0.25～0.77),患病与S/LA基因型成负关联(OR=0.44,95%CI:0.24～0.81)。结论::5-HTTLPR基因启动子区域多态性与中国汉族人群AN可能存在关联,L、LA等位基因及L/S、S/LA基因型为AN患病的保护等位基因及基因型。     

中国汉族人群5-羟色胺转运体基因多态性与非病灶性颞叶癫痫的关联性

目的　初步探讨颞叶癫痫(temporal lobe epilepsy,TLE)的遗传易感因素。方法　采用聚合酶链反应技术,检测263例TLE患者和296名健康对照者的5-羟色胺转运体(5-hydroxytryptamine transporter,5-HTT) 基因启动子的基因连锁多态区(gene-linked polymorphic region,LPR) 和第2内含子的可变数目串联重复区(variable number tandem repeat,VNTR) 多态性,分别对所得基因型和等位基因的频率进行相关统计学分析。结果　TLE患者5-HTTLPR多态性的基因型和等位基因频率与正常对照组之间的差异无统计学意义(P>0.05)。TLE患者的5-HTTVNTR的基因型12/12频率高于正常对照组(P<0.01),其等位基因12的频率高于正常对照组(P< 0.01)。携12等位基因者患TLE的相对危险度(OR)是1.435,95%可信区间(CI)为1.096～1.880(P<0.05)。 结论　5-HTTLPR可能不是TLE患者的遗传位点,第2内含子VNTR的等位基因12可能与TLE有一定的关联。     

Reduced hippocampal volumes associated with the long variant of the serotonin transporter polymorphism in major depression

BACKGROUND: Substantial evidence supports a role for dysfunction of the serotonin transporter in the pathogenesis of major depression. Several studies have found reciprocal interactions between the serotonergic system and both brain-derived neurotrophic factor and glutamate, which are known to modulate or affect hippocampal morphologic characteristics. OBJECTIVE: To examine the influence of a polymorphism (5-HTTLPR) in the promoter region of the serotonin transporter gene on hippocampal volumes in patients with major depression and healthy controls. DESIGN: Baseline investigation of a prospective magnetic resonance imaging study with a 4-year follow-up period. PATIENTS: We examined 40 inpatients with major depression as well as 40 healthy controls matched for age, sex, and handedness. MAIN OUTCOME MEASURES: Subjects underwent high-resolution magnetic resonance imaging. Furthermore, genotyping for the 5-HTTLPR biallelic polymorphism was performed, which consists of a 44-base pair insertion (L allele) or deletion (S allele). RESULTS: Patients with the L/L homozygous genotype had significantly smaller hippocampal gray matter (left hemisphere: P=.003; right hemisphere: P=.01) and white matter volumes (left hemisphere: P=.001; right hemisphere: P=.002) than controls with this genotype. No significant differences were found between patients and controls with the L/S or S/S genotype. Moreover, patients with the L/L genotype had significantly smaller hippocampal white matter volumes than those with the L/S or S/S genotype (P=.03). CONCLUSIONS: These findings suggest that homozygosity for the L allele is associated with decreased hippocampal volumes in patients with major depression but not in healthy controls. A possible explanation is that the interaction between the serotonergic system and neurotrophic factors as well as excitatory amino acid neurotransmission may affect hippocampal morphologic characteristics.     

Serotonin transporter gene polymorphism and schizoid personality traits in the patients with psychosis and psychiatrically well subjects.

BACKGROUND AND OBJECTIVES: serotonin transporter (5-HTT) gene allelic variants were shown to be associated with Neuroticism and Harm Avoidance but the results were not replicated in other studies. The current investigation was undertaken in a further attempt to study the relationship between 5-HTT polymorphism and personality traits. SUBJECTS AND METHODS: to evaluate a spectrum of personality traits, MMPI was administered to a sample including patients with affective disorders (n=114), patients with schizophrenia spectrum illnesses (n=110) and psychiatrically well controls (n=124). All groups were genotyped for VNTR-17 and functional insertion-deletion (5-HTTLPR) polymorphisms. RESULTS: an association was found between 5-HTTLPR polymorphism and scores on three MMPI scales: Psychopathic deviance, Paranoia and Schizophrenia in patients with affective disorders and S chizophrenia in normal subjects. Both affected and control individuals with 'ss' genotype exhibited lower scores on these scales. CONCLUSION: we demonstrated that functional deletion/insertion allelic variation associated with decreased expression of serotonin transporter ('s' allele or 'ss' genotype) may restrict expression of schizoid traits in normal subjects and patients with affective disorders.     

Serotonin transporter polymorphisms and persistent, pervasive childhood aggression

OBJECTIVE: The purpose of this study was to examine the potential association of the serotonin transporter (5-HTT) gene and childhood aggression by testing the 5-HTT variable-number-tandem-repeat and serotonin transporter promoter polymorphism (5-HTTLPR), including the recently discovered Lg allelic variant of 5-HTTLPR. METHOD: Clinically referred children displaying extreme aggression, with a minimum 2-year history, were genotyped for 5-HTTLPR (N=77) and 5-HTT variable-number-tandem-repeat (N=78). Analyses compared genotype frequencies of the aggressive children with healthy comparison subjects. RESULTS: The "low expressing" genotypic variants of the 5-HTTLPR polymorphism (S/S, Lg/S, Lg/Lg) were significantly associated with childhood aggression. CONCLUSIONS: This is the first study to report a significant association between the 5-HTTLPR gene and childhood aggression.