DRD4 exon Ⅲ基因多态性与精神分裂症患者攻击行为及精神症状的关联研究

Relationship between dopamine receptor D4 exon Ⅲ polymorphism and aggressive behavior and psychiatric symptoms in schizophrenia

目的了解多巴胺D4受体(DRD4)基因第3外显子48 bp可重复序列多态性(DRD4exonⅢ48 bp VNTR)与精神分裂症攻击行为及精神症状之间的关系。方法选取符合国际疾病分类第10版(ICD-10)精神分裂症诊断标准的患者302例,按修改版外显攻击行为量表(MOAS)得分进行分组,分别进行一般人口学资料、阳性和阴性症状量表(PANSS)测定,采用聚合酶链反应(PCR)等位基因分型技术检测DRD4 exonⅢ48 bp VNTR多态位点。用SHEsis软件进行基因型Hardy-Weinberg遗传平衡度检验及组间基因型频率的差异,用χ2检验和t检验分析DRD4基因与精神分裂症攻击行为及精神症状之间的关系。结果两组间一般人口学资料差异无统计学意义(P>0.05)。两组DRD4基因型频率均符合Hardy-Weinberg遗传平衡定律(P>0.05)。共检测到DRD4exonⅢ48 bp VNTR的6种等位基因和8种基因型,两组最常见的是4次重复等位基因。两组DRD4基因的基因型及等位基因的频率分布的差异有统计学意义(P<0.05)。研究组携带长重复等位基因组(49例)与短重复等位基因组(85例)PANSS分量表分和因子分比较,PANSS分量表分差异均无统计学意义(P>0.05),因子分中思维障碍和攻击性差异有统计学意义(P<0.05),长重复等位基因组高于短重复等位基因组。结论 (1)DRD4 exonⅢ48 bp VNTR与精神分裂症攻击行为之间存在关联。(2)DRD4 exonⅢ48 bp VNTR与精神分裂症攻击行为患者思维障碍和攻击性存在关联,携带长重复等位基因患者的症状可能较严重。

Objective To investigate the relationship between the polymorphism of repeatable sequence of DRD4 exon Ⅲ 48 bp gene and psychiatric symptoms and aggressive behavior in schizophrenia. Methods 302 patients who were diagnosed as schizophrenia according to the criteria of the International classification of diseases(ICD-10) were divided into two groups according to the score of modified overt aggression scale(MOAS): group with aggressive behavior(research group) and group without aggressive behavior(control group). All objects were evaluated with general demographic data and positive and negative syndrome scale(PANSS). The polymorphous points of DRD4 gene were genotyped by the amplification refractory mutation system(ARMS) polymerase chain reaction(PCR) genotyping assay method. The test for Hardy-Weinberg equilibrium and the difference of genotype frequency between groups were performed using SHEsis software, the significance for the association was estimated by chi-square and t test. Results In those common items, there were no significantly differences between the two groups(P>0.05). The DRD4 genotype frequencies of the two groups were consistent with the Hardy-Weinberg genetic equilibrium law(P>0.05). Six alleles and eight genetypes of 48 bp polymorphism had been detected in the exon Ⅲ of DRD4. In all the groups, the most common allele was 4. There were statistical differences on the frequencies of genotypes and alleles of DRD4 exon Ⅲ bp VNTR among the two groups(P<0.05). The differences of PANSS subscale scores between 49 patients who carried long repeat allele group and 85 patients who carried short repeat allele group were not statistically significant in research group(P>0.05). The factor scores of thought disorder and aggressivity were statistically significant(P<0.05). The scores in patients who carried long repeat allele group were higher than that in short repeat allele group. Conclusions(1) The results suggest that the DRD4 exon Ⅲ 48 bp VNTR is associated with aggressive schizophrenic patients.(2) The DRD4 exon Ⅲ 48 bp VNTR is associated with thought disorder and aggressivity in aggressive schizophrenic patients. The aggressive schizophrenic patients who carried long repeat alleles may have more serious psychiatric symptoms