目的:为了探索精神分裂症的病因,将分裂样特质作为“内表型”进行遗传学分析,研究儿茶酚氧位甲基转移酶(COMT)、脯氨酸脱氢酶(PRODH)、脑源性神经营养因子(BDNF)基因与分裂样特质的相关性,为寻找精神分裂症的相关候选基因提供资料。方法:以性别、年龄和受教育年限作为限制因素,在成都市5城区随机抽取了465名健康成年人纳入研究,采用分裂样人格问卷(SPQ)进行人格评定。用SPSS11.0软件对人组者的性别、年龄和受教育年限与SPQ相关得分进行回归分析。采用QTPHASE软件分别对COMT(rs4680G/A、rs165599G/A)、PRODH(1852G/A、1945G/A)、BDNF(rs6265)基因和SPQ的相关得分进行等位基因、单倍型的定量相关分析;采用方差分析进行基因型与分裂样特质的相关分析。结果:受教育年限与SPQ的7个亚量表分(牵连观念、奇怪的信念或怪异的思维除外)、3个因子分和总分均存在相关性得分随着受教育年限的增加而减少。多重检验校正前COMT rs4680G/A与怪异言语(配对等位基因P=0.04;配对基因型P=0.049)、多疑亚量表(配对基因型P=0.024)均存在相关;BDNF rs6265与因子2人际关系存在相关(配对基因型P=0.027)。多重检验校正后则上述相关性消失。另外,仅在男性个体中发现COMT rs4680G/A与SPQ总分、瓦解因子、情感狭窄亚量表相关。结论:COMT rs4680G/A可能与男性分裂样特质之间存在相关性。
Objective: In order to explore the etiology of schizophrenia, to regard schizoid trait as endophenotype to do genetics analysis. Correlation between schizoid trait and gene of catechol-o-methyltransferase (COMT), proline dehydrogenase (PRODH) and brain-derived neurotrophic factor (BDNF) were studied to provide related data for searching candidate genes of schizophrenia. Method: Using gender, age and education years as limitation factors, 465 healthy adults were randomly selected from 5 city zones in Chengdu and enrolled in the study. Schizotypal personality questionnaire (SPQ) was used to evaluate the personality. Regression analysis was conducted between patients' gender, age, education years and the related scores of SPQ by SPSS 11.0 software. Quantitative analysis of allele and haplotype was done between gene of COMT (rs4680G/A, rs165599G/A), PRODH( 1852G/A, 1945G/A)and BDNF (rs6265) and the related scores of SPQ respectively by QTPHASE software. Correlated analysis was conducted between genotype and schizoid trait by analysis of variance. Results:There was a correlation between education years and seven subscales, three factor scores and the total score of SPQ respectively. The scores above decreased along with the increase of education years. Before correction for multiple testing, there was a relationship between COMT rs4680G/A and weird spech (allele-wise, P = 0,04; genotype-wise, P = 0.049) and suspiciousness subscale (genotype-wise, P = 0. 024 ). And BDNF rs6265 was related to factor 2 interpersonal measure ( genotype- wise, P = 0.027). The correlation above would disappear after correction for multiple testing, it was found only in male COMT rs4680G/A correlated with the total score, disorganization factor and subscale of constricted emotion of SPQ. Conclusion: COMT rs4680G/A may be associated with nkale schizoid trait.