DXS7基因座的多态性与单相抑郁症

目的　本工作旨在研究单相型抑郁症与 Ｘ 染色体上 Ｄ Ｘ Ｓ７ 基因座多态性间的遗传关联。方法　应用 Ｐ Ｃ Ｒ 扩增片段长度多态性（ Ａｍｐ Ｆ Ｌ Ｐ） 研究６６ 例单相型抑郁症中 Ｄ Ｘ Ｓ７ 基因座的多态性分布。结果　在６６ 例患者和８５ 名正常人中观察到 Ｄ Ｘ Ｓ７ 基因座有４ 种等位基因,片段大小为１５７ ～１６７ ｂｐ ,经比较多态性分布表明患者与正常人间在频率分布上无显著性差异,但是在早发型抑郁症和迟发型抑郁症间有差异。结论　迟发型抑郁症与 Ｄ Ｘ Ｓ７ 基因座的１６５ ｂｐ 等位基因呈显著性关联（ Ｒ Ｒ＝ ２０８ , Ｐ＜ ００５） 。     

应用PCR—DG GE方法检测脆性X位点FMR—1基因内CGG重复序列

脆性Ｘ综合下是一最常见的Ｘ性连锁的遗传智力低下病，是因Ｘ染色体上脆性部位的ＦＭＲ－１基因内一段不稳定的ＣＧＧ重复序列的异常扩增所致，本文建立了多聚酶链反应－变性工聚丙烯酰胺凝胶电泳（ＰＣＲ－ＤＧＧＥ）的方法，并成功地检测出８３例正常人Ｘ染色体脆性位点ＦＭＲ－１基因内ＣＧＧ重复序列片段。在上述８３例正常人中发现有１６个不同在小的等位基因，说明该重复序列的长度在中国人中具有丰富的多态性，最常见的等位基     

髓鞘碱性蛋白基因与多发性硬化相关性的研究

目的探讨中国人群中多发性硬化（ＭＳ）的遗传易患性与髓鞘碱性蛋白基因５′端四核苷酸重复序列多态性的相关性。方法以２８例确诊ＭＳ患者及４７名正常对照为研究对象,从外周血白细胞中提取ＤＮＡ,利用聚合酶链反应技术特异性扩增ＭＢＰ基因５′端四核苷酸重复序列,并通过琼脂糖凝胶电泳分析扩增产物的多态性。结果发现四种等位基因,片段大小为１．０６ｋｂ,０．９８ｋｂ,０．６１ｋｂ和０．５４ｋｂ,以前两种多见。１．０６ｋｂ基因片段在女性中出现频率很高,达７３％,ＭＳ组与对照组无差别。男性中１．０６ｋｂ基因片段出现频率ＭＳ组（６９％）明显高于对照组（３９％）。ＭＳ组中等位基因的分布无性别差异。结论中国人群中ＭＢＰ基因第一个外显子５′端四核苷酸重复序列多态位点等位基因的分布有性别差异,１．０６ｋｂ的等位基因片段可能与ＭＳ易患性相关。     

缺血性脑血管病患者载脂蛋白B基因多态性与血脂关系探讨

应用聚合酶链反应（ＰＣＲ），检测了１０６例正常汉族人及５５例缺血性脑血管病（ＩＣＶＤ）病人的ａｐｏＢ基因ｘｂａⅠ酶切位点限制性片段长度多态性（ＲＦＬＰｓ）及其与血脂的关系。结果表明ＩＣＶＤ组ｘｂａⅠ酶切位点上Ｘ＋的等位基因频率明显高于正常对照组（Ｐ＜０．００５）；ＩＣＶＤ组中具Ｘ＋Ｘ－基因型者的血浆ＨＤＬ－Ｃ较Ｘ－Ｘ－基因型者明显降低（Ｐ＜０．０５），而ＬＰ（ａ）和ＴＣ明显增高（Ｐ＜０．０５～０．００５）。提示ａｐｏＢ基因多态分析结合血浆脂蛋白测定更能有效地检测ＩＣＶＤ易患人群。     

细胞色素P4502D6基因XbaⅠ限制性片段长度多态性及点突变与帕 …

目的探讨机体的第Ⅰ相解毒系统障碍与帕金森病遗传易患性的关系。方法 选择ＰＤ病人１００例和正常人１００名，利用ＸｂａⅠ限制性片段长度多态性和ＰＣＲ－ＲＦＬＰ技术，检测细胞色素Ｐ４５０２Ｄ６基因的突变。比较ＰＤ病人与正常人之间多态性频率的差异。结果 ＸｂａＩＲＦＬＰ分析可见ＰＤ病人组４４ｋｂ等位基因频率，以及４４ｋｂ／４４ｋｂ纯合子的频率高于正常对照组，而且在病人组，Ａ，Ｂ，Ｃ１８８→Ｔ，Ｃ４２６８→     

早老素1基因多态性与迟发性阿尔茨海默病的遗传相关研究

目的 对中国广州汉族人群的早老素１（ＰＳ１）基因内含子８多态性与迟发性阿尔茨海默病（ＡＤ）进行关联分析。方法 应用聚合酶链反应和限制性片段长度多态性方法,检测１０４例迟发性ＡＤ患者（ＡＤ组）和１０６名正常老年人（对照组）的ＰＳ１基因内含子８的多态性,并对ＡＤ与ＰＳ１基因各等位基因及基因型进行了关联分析。结果 （１）ＡＤ患者组的ＰＳＩ等位基因１的频率（０．６０）高于对照组（０．４８）,等位基因２的频     

精神分裂症患病同胞基因型配对分析研究

为验证精神分裂症基因位于性染色体假常染色体区域的假说，选取了７３组精神分裂症患病同胞和其父母为试验对象，以位于性染色体假常染色体区域ＤＸＹＳ１４基因座的探针ｐ２９Ｃ１进行了限制性片断长度多态性的探测，并以该探针划分的单体型进行了患病同胞基因型配对分析。在ＤＸＹＳ１４基因座附近，父母的等位基因在精神分裂症患病同胞中的分离与假设无连锁前提下的理论预计有明显的差异（Ｐ＝０．００８７）。此试验结果在一定程度上支持精神分裂症基因位于性染色体假常染色体区域的假说     

Ⅱ型糖尿病伴脑梗死病人血浆氧化修饰低密度脂蛋白测定的意义

探讨血浆氧化修饰低密度脂蛋白水平的变化与Ⅱ型糖尿病（ＤＭ）伴脑梗死（ＣＩ）的关系。方法：应用ＥＬＩＳＡ法测定ＤＭ伴ＣＩ病人血浆ＯＸＬＤＬ的水平,另设单纯性ＣＩ组及正常对照组。结果（１）无论是否合并ＤＭ,ＣＩ组病人血浆ＯＸＬＤＬ水平较正常对照组明显增高;且ＤＭ伴ＣＩ组明显高于单纯于ＣＩ组。（２）血浆ＯＸＬＤＬ水平与ＬＤＬ－Ｃ、ａｐｏＢ水平呈正相关,而与ＨＤＬ－Ｃ水平呈负相关。结论：ＯＸＬＤＬ在ＤＭ伴     

细胞色素P450_2D_6基因Xba I 限制性片段长度多态性及点突变与帕金森病的关系

目的探讨机体的第Ｉ相解毒系统障碍与帕金森病（ＰＤ）遗传易患性的关系。方法选择ＰＤ病人１００例和正常人１００名，利用ＸｂａＩ限制性片段长度多态性（ＲＦＬＰ）和ＰＣＲＲＦＬＰ技术，检测细胞色素Ｐ４５０２Ｄ６（ＣＹＰ２Ｄ６）基因的突变。比较ＰＤ病人与正常人之间多态性频率的差异。结果ＸｂａＩＲＦＬＰ分析可见ＰＤ病人组４４ｋｂ等位基因频率，以及４４ｋｂ／４４ｋｂ纯合子的频率高于正常对照组，而且在病人组Ａ、Ｂ、Ｃ１８８→Ｔ、Ｃ４２６８→Ｃ、Ｃ２９３８→Ｔ点突变频率也高于正常对照组，使患ＰＤ的危险性提高，危险度达２０倍左右。结论解毒酶ＣＹＰ２Ｄ６基因突变增加患ＰＤ的危险性。这提示解毒酶缺陷可能是ＰＤ遗传易患性的重要原因。     

急性脑梗塞患者红细胞流变特性改变及己酮可可碱干预研究

目的探讨急性脑梗塞（ＡＣＩ）患者红细胞流变特性的变化及己酮可可碱（ＰＴＸ）干预治疗的效应。方法采用激光衍射法等方法测定了４６例ＡＣＩ患者的红细胞流变学指标，与２２例正常人对照；并随机将患者分为ＰＴＸ组和低分子右旋糖酐（ＬＭＤ）＋乙酰水杨酸（ＡＳＡ）组对照干预治疗。结果ＡＣＩ患者红细胞流变学指标显著异常，且红细胞变形指数（ＤＩ）与患者神经功能缺损评分（ＮＤＳ）呈显著负相关。用药后两组红细胞流变学指标及ＮＤＳ均有显著改善，随用药时间的延长，ＰＴＸ组改善红细胞变形性（ＥＤ）和减轻患者ＮＤＳ优于ＬＭＤ＋ＡＳＡ联合组。结论红细胞流变特性异常尤其ＥＤ降低是脑梗塞病理生理过程中的重要因素之一，并对患者的病情发展和预后具有重要影响。ＰＴＸ可能是脑梗塞治疗的有效药物之一。     

儿茶酚氧位甲基转移酶基因多态性与心境障碍的关联研究

目的 探讨中国汉族人22号染色体儿茶酚O-甲基转移酶(COMT)基因与心境障碍(MD)的关系。方法 应用聚合酶链反应和限制性片段长度多态性技术，检测90例MD患者(患者组)、90名正常人(对照组)及5个MD高发家系(共25名成员)的COMT基因多态性；用改进的传递/不平衡(TDT)方法分析5个高发家系COMT基因与MD的关系。结果 (1)患者组COMT等位基因A频率(22．78％)低于对照组(35．00％)，等位基因G频率(77．22％)高于对照组(65．00％)，差异均有非常显著性(P＝0．01)。按性别比较，等位基因A和G频率在两组男性之间的差异均无显著性(P＝0．10)，而两组女性间的差异则具显著性(P＜0．01)。(2)COMT基因A／A基因型频率两组的差异无统计学意义(P＝0．73)；但患者组及其男性和女性的A／G基因型频率(分别为34．44％、33．33％和35．56％)均低于对照组(分别为61．11％、60．00％和62．22％；P＝0．00)；患者组及其男性和女性的G／G基因型频率(分别为60．00％、60．00％和60．00％)均高于对照组(分别为34．44％、35．56％和33．33％；P＝0．00、P＝0．02和P＝0．01)。(3)用TDT方法分析，5个MD高发家系COMT基因与MD存在关联(P＝0．04)。结论 MD患者组与正常对照组的COMT基因多态性存在差异；中国汉族人22号染色体可能存在心境障碍易患性基因。     

Influence of 5-HTTLPR and TPH variants on illness time course in mood disorders

The aim of our study was to investigate gene variants in the long-term outcome of mood disorders. We retrospectively studied a sample of inpatients affected by recurrent and rapid cycling mood disorders. The serotonin transporter gene-linked functional polymorphic region (5-HTTLPR) and the A218C tryptophan hydroxylase (TPH) gene variant were determined using a PCR-based technique. For 5-HTTLPR polymorphism we genotyped 435 inpatients affected by major depressive (n=153), bipolar (n=213) and rapid cycling (n=69) mood disorders and 456 controls; for TPH we genotyped 399 inpatients (MD, n=132; BP, n=203; rapid cycling n=64) and 259 controls. Random Regression Model analysis was used to investigate the longitudinal time course of the illness. 5-HTTLPR and TPH polymorphisms were not associated with mood disorders time course. However we observed an excess of 5-HTTLPR*long alleles among rapid cycling subjects compared to both controls (P=0.018) and remitting mood disorders (P=0.006). TPH frequencies did not differ between mood disorders subtypes. Our results suggest that 5-HTTLPR variants may confer a susceptibility toward rapid cycling mood disorders.     

精神分裂症和心境障碍混合家系5-HTR 6基因多态性的关联分析

目的 在中国汉族人群精神分裂症和心境障碍混合家系中探讨五羟色胺6受体（5-HTR6）基因267C／T多态性与精神分裂症、心境障碍的关联性。方法 采用聚合酶链反应一限制性片断长度多态（PCR—RFLP）技术对67例精神病混合家系患者及其父母进行5-HTR6基因267C／T多态性检测,并予以传递不平衡检验（TDT）。结果 患者组与父母组之间,5-HTR6基因267C／T多态性等位基因分布（χ^2=2．70,v=1,P〉0．05）和基因型分布（χ^2=2．97,v=2,P〉0．05）无明显差异,5-HTR6基因267C／T多态性与精神分裂症（χ^2=5．16,P〈0．05）存在关联,但与心境障碍（χ^2=2．17,P〉0．05）无关联。结论 在中国汉族人群中5-HTR6基因或邻近基因可能是精神分裂症易患基因之一,但可能不是心境障碍的易患基因。     

A novel allele in the promoter region of the human serotonin transporter gene

The human serotonin transporter (hSERT) gene is a promising candidate for mediating the genetic susceptibility for various psychiatric conditions such as mood and obsessive-compulsive disorders. Two polymorphic sites in this gene attracted much interest: a VNTR of 17-bp repeats in intron two, and an insertion/deletion in the 5'-flanking promoter region (5-HTT gene-linked polymorphic region-5-HTTLPR) creating a short (S) and a long (L) allele. The 5-HTTLPR polymorphism is situated in a GC-rich region composed of 20-23 bp repeating units. The S and L alleles have 14 and 16 repeat-elements respectively. Positive associations of the 5-HTTLPR polymorphism with mood disorders, anxiety-related personality traits, autism and late-onset Alzheimer's disease have been published, although some non replications were also reported. Here we report a novel allele (termed LJ) in the 5-HTTLPR site. This allele is longer than the L allele by 43 bp, has 18 repeat units and contains two copies of the insertion/deletion sequence arranged in tandem. The LJ allele was found in individuals of Libyan and Tunisian Jewish origin but not in Moroccan or Ashkenazi Jews.     

Autism spectrum disorders associated with X chromosome markers in French-Canadian males

It is now well established that genetic factors play an important role in the pathogenesis of autism disorder and converging lines of evidence suggest the implication of the X chromosome. Using a sample of subjects diagnosed with autism spectrum disorders, exclusively composed of males from French-Canadian (FC) origin, we tested markers covering the entire X chromosome using a family-based association study. Our initial analysis revealed the presence of association at two loci: DXS6789 (P=0.026) and DXS8043 (P=0.0101). In a second step, we added support to the association at DXS8043 using additional markers, additional subjects and a haplotype-based analysis (best obtained P-value=0.00001). These results provide support for the existence of a locus on the X chromosome that predisposes the FC to autism spectrum disorders.     

DXS7基因座的多态性与精神疾病的关联分析

目的 探讨DXS7基因座多态性与精神分裂症、单相抑郁症、双相情感障碍和Alzheimer病的关联。方法 应用Amp-FLP技术,对上海地区汉族人群中157例精神分裂症、62例单相抑郁症、61例双相情感障碍和58例Alzheimer病患者与DXS7基因座多态性进行遗传关联分析。结果(1)4种精神病与DXS7基因座多态性间无关联。(2)在男性精神分裂症患者,159bp等位基因和男性Alzheimer病患者的167bP等位基因的频率与男性对照组有差异,Z值分别为2.36和 2.10,P值均小于0.05。(3)经OR值计算,OR分别为4.93和0.22,但是这两个OR值均无显著性意义(P>0.05)。结论 人类X染色体短臂(Xp)上DXS7基因座附近可能不存在这4种精神病的易感位点。     

Association study of serotonin transporter gene VNTR polymorphism and mood disorders,onset age and suicide attempts in a Chinese sample

The human serotonin transporter (5-HTT) gene is an important candidate for the pathogenesis of mood disorders. Associations have been reported between a variable-number tandem-repeat polymorphism in intron 2 of the serotonin transporter gene (5-HTTVNTR) and mood disorders in a number of studies of Western and Chinese populations. However, no such relationships have been determined in other analogous research. To replicate these positive findings in a Chinese population and to determine the association between onset age of bipolar disorder and 5-HTTVNTR, we investigated the prevalence of this polymorphism in an independent Chinese population (83 bipolar disorder patients, 77 major depressive disorder patients and 169 controls), demonstrating no significant association between the 5-HTTVNTR polymorphism and mood disorders or age at onset. Further, no association was demonstrated between this polymorphism and suicidal history in mood disorder patients. These negative findings suggest that 5-HTTVNTR does not play a major role in the pathogenesis of mood disorder in Chinese populations.     

Quinone oxidoreductase (NQO1) gene polymorphism may not confer a susceptibility to mood disorders

Quinone oxidoreductase (NQO1) plays a key role in the cellular antioxidant defense by detoxifying quinine derivatives. Case-control association study of the possible relationship between the NQO1 gene polymorphism and mood disorders (patients with major depressive disorder, n=61; patients with bipolar I disorder, n=80; control, n=106) was carried out using PCR-based techniques. These preliminary results showed that the NQO1 gene polymorphism was not related to a susceptibility to mood disorders.     

Cholecystokinin- and cholecystokinin-B-receptor gene polymorphisms in panic disorder

Panic disorder like other neuropsychiatric disorders is believed to be caused by multiple psychosocial and biological factors. Several lines of evidence point to a role for the peptide neurotransmitter cholecystokinin in the pathogenesis of panic disorder. We therefore determined the allele and genotype frequencies of a single nucleotide polymorphism in the CCK gene (-36C>T) and one CT repeat polymorphism in the CCK-B-receptor gene in a German panic disorder sample (n = 115 for CCK gene polymorphism, n = 111 for CCK-B-receptor polymorphism) and compared them with gender and age matched controls. The length of the polymorphic CT repeat alleles varies between 146 bp and 180 bp. We first analysed the results by a permutation test which provided evidence for heterogeneity between patients and controls (p=0.002). We then analysed the data as a di-allelic polymorphism with a short (146-162bp) and a long (164-180bp) allele and as a tetra-allelic polymorphism with 4 alleles (146-154bp, 156-162bp, 164-170bp, 172-180bp). In the di-allelic analysis as well as in the tetra-allelic analysis there was an excess of the longer allele (p = 0.001) or the two longer alleles (p = 0.041) respectively in patients with panic disorder. No difference between groups was observed for the -36C > T polymorphism. Our findings are consistent with the notion that genetic variation in the CCK neurotransmitter system contributes to the pathogenesis of panic disorder.