随机人群与精神分裂症患者微卫星DNA vWA多态性的关联性分析(英文)

Polymorphism of microsatellite DNA vWA in random population and schizophrenic patients

背景:精神分裂症的发病与遗传关系密切,但对相关基因定位相当困难,因此有必要先寻找有关遗传标志。目的:通过对微卫星DNA vW A 多态性的分析,了解精神分裂症与vW A有关等位基因的关联情况。设计:以精神分裂症患者和随机人群为观察对象的病例-对照研究。单位:大连市第七人民医院病房和大连医科大学分子生物学实验室。对象:精神分裂症病例为2002-03/07大连市第七人民医院(精神病专科医院)住院患者32例,诊断符合《美国精神疾病诊断统计手册》第3版精神分裂症诊断标准,临床表现以阴性症状为主。随机人群样本为在大连市红十字血液中心随机选取的正常人血液样本123份,无精神疾病和严重躯体疾病,无明确亲缘关系。方法:采取抗凝全血标本,用PE Profilerplus 系统进行聚合酶链反应复合扩增,然后用ABI310型基因分析系统对扩增产物进行电泳和基因检测。计算出各等位基因的基因频率,并按H ardy-W einberg平衡定律计算出各等位基因的理论频率与实际观测值,作吻合度检验和连锁分析;将精神分裂症患者与随机人群进行比较,按RR =Pd ×(1-Pc)/Pc ×(1-Pd)公式进行相对危险度分析并作统计学显著性检验(RR:相对危险度;Pd:精神分裂症患者基因频率;Pc:随机人群基因频率),RR >1为有易感倾向,RR <1为有抗性倾向。找出vW A 与精神分裂症相关基因的易感连锁或抗性连锁的等位基因。主要观察指标:主要结局:精神分裂症患者与随机人群vW A 等位基因关联性分析。次要结局:精神分裂症患者和随机人群vW A 等位基因频率与H ardy-W einberg定律的吻合度。结果:两组受试对象的测试样本均纳入结果分析。①精神分裂症患者和随机人群vW A 等位基因频率符合H ardy-W einberg平衡定律(P >0.05)。②精神分裂症患者vW A-14的检出率(17.2%)低于随机人群(33.3%),差异有显著性(RR=0.415,P=0.014);精神分裂症患者vW A-17的检出率(31.3%)高于随机人群(19.5%),差异有显著性(RR =1.866,P =0.043);其他各等位基因检出率差异无显著性(P >0.05)。结论:精神分裂症患者vW A-14的检出率显著低于随机人群,提示vW A-14在精神分裂症时可能会因某种原因而被负选择,其附近可能存在抵抗精神分裂症发病的基因。精神分裂症患者vW A-17的检出率显著高于随机人群,表明vW A-17与精神分裂症相关联,其附近可能存在精神分裂症易感基因。

BACKGROUND： Schizophrenia is substantially heritable, but specific susceptibility genes remain difficult to be identified. Therefore, it is necessary to explore hereditary markers first. OBJECTIVE： To investigate the relationship between schizophrenia and related vWA allele genes based on the analysis of microsatellite DNA vWA polymorphism. DESIGN： A case-controlled study with schizophrenic patients and randomly selected population as subjects. SETTING： Ward of Dalian Seventh People＇ s Hospital and Molecular Bi- ological Laboratory of Dalian Medical University. PARTICIPANTS： Totally 32 schizophrenic patients received treatment between March and July 2002 at Dalian Seventh People＇s Hospital which specializes in schizophrenia. Schizophrenia was diagnosed according to the diagnostie standard of the third edition of “the American Diagnostic Statistical Manual for Schizophrenic Diseases”, and their clinical manifestations were predominantly negative signs. Altogether 123 normal blood samples were collected from random population at the Blood Center of Dalian Red Cross. They all denied psychological ailments and severe systematic diseases, and they had no kinship with each other. METHODS： Heparin anti-coagulation blood samples were collected and PCR compound amplification was carried out with the aid of PE Profiler plus system. Then the products were subjected to electrophoresis and gene detection with AB1310 type gene analysis system so as to calculate the frequency of allele genes; Hardy-Weinberg equation law was used to make coincidence test and linkage analysis of the theoretical frequency and actual one. Schizophrenic patients and random population were compared and relative risk was calculated with RR=Pd × （1-Pc）/Pc × （1-Pd） in order to assess the statistical significance （RR： relative risk; Pd： gene frequency of schizophrenia; Pc： gene frequency of random population）. RR 〉 1 was considered of higher susceptibility while RR 〈 1 was considered of anti-susceptibility. In this way, we could tlnd out vWA allele genes that had susceptible linkage or anti-linkage with schizophrenic related genes. MAIN OUTCOME MEASURES： Major outcome： Correlation analysis of vWA allele genes in schizophrenic patients and random population. Secondary outcome： The coincidence of vWA allele gene frequency in patients with schizophrenia and random population with what was calculated by Hardy-Weinberg law. RESULTS： Data of the two groups were processed according to the objective and statistically analyzed. ①vWA allele gene frequency in patients with schizophrenia and in random population was found to coincide with HardyWeinberg law （P 〉 0.05）. ②The positive rate of vWA-14 in schizophrenic patients （17.2%） was obviously different from that in random population （33.3%） （RR=0.415, P=0.014）. The positive rate of vWA-17 in schizophrenic patients （31.3%） was found to be significantly higher than that in random population （19.5%） （RR=1.866, P=0.043） while it did not differ significantly in other allele genes （P 〉 0.05）. CONCLUSION： The positive rate of vWA-14 was significantly lower in schizophrenic patients than in random population, indicating that vWA-14 locus may be negatively selected in schizophrenia due to some reasons, which may＇ be approximate to antischizophrenia genes. Moreover, the higher expression of vWA-17 in schizophrenic patients than in random population suggests that vWA-17 locus is correlated with schizophrenia, which may be. approximate to sehizophreniasusceptibile genes.