精神分裂症与多巴胺D_4受体基因及载脂蛋白E基因的关联分析

An analysis of association between dopamine D_4 receptor gene and apolipoprotein E gene and schizophrenia

目的 探讨上海地区汉族人群载脂蛋白E(apoE)基因、多巴胺D4 受体 (DRD4)基因与精神分裂症的易患性、患者的性别、发病年龄以及病程之间的关系。方法 应用聚合酶链反应扩增技术及限制性片段长度多态性对 80例精神分裂症患者和 80名正常人分别测定apoE、D4基因型和等位基因。结果 (1 )患者组apoE等位基因ε2 频率明显高于对照组 ,与精神分裂症呈显著正关联 [相对危险度 (RR) =2 0 1 ,P <0 0 5] ;而且患者组男性等位基因ε2 频率明显高于对照组男性 ,与精神分裂症呈显著正关联 (RR =8 5l,P <0 0 5)。 (2 )DRD4基因与精神分裂症无关联 ,但是发病年龄与A2 ,A4等位基因及性别与 4/ 4基因型有关联 (P <0 0 5) ;(3)患者组与对照组携带ε4 与非携带ε4 间比较 ,DRD4基因的基因型和等位基因频率均无差异。患者组和对照组的组内携带ε4 与非携带ε4 间比较的差异均有显著性 ,对照组携带ε4 组的DRD4基因型 4/ 4 (85 % )和等位基因A4(89% )频率均明显高于非携带ε4组 (55 % ,67% ) ,而非携带ε4 组的等位基因A2 (2 9% )频率高于携带ε4 组 (1 2 % ) ;患者组非携带ε4 组的DRD4基因型 2 / 2 (1 3 % )和等位基因A2 (2 4 % )频率均高于携带ε4 组 (0 % ,8% )。结论 (1 )

Objective To detect the relation between dopamine receptor 4 (DRD4) gene, apolipoprotein E (apoE) gene and the susceptibility, the sex, the age of onset, course of schizophrenia in Shanghai Methods The genotypes and alleles of DRD 4 receptor gene and apoE gene in 80 schizophrenic patients and 80 normal controls were examined with polymerase chain reaction and restriction fragment length polymorphism techniques Results (1) There was an positive association between apoE ε 2 alleles gene and susceptibility of schizophrenia( RR =2 01, P <0 05), and the frequency of allele ε 2 was more higher in male patients than in male controls ( RR =8 51, P <0 01) (2) DRD4 was not related to schizophrenia, but allele A2, A4 and genotype 4/4 was associates with age of onset and gender of the patients ( P <0 05) (3) The distributions of the DRD4 genotypes and alleles between patients with ε 4 and without ε 4 were not significantly different compared with the controls, but significantly different within the patient or control group Conclusions (1) ApoE gene may affect the susceptibility of schizophrenia, but not the age of onset and course of illness (2) DRD4 gene may be related to the age of onset in the patients (3) The frequency distribution of apoE gene polymorphism may be different between the genders of patients (4) apoE gene may be correlated with DRD4 gene