LINKAGESTUDIES ON FAMILIES WITH MULTIPLE MEMBERS OF SCHIZOPHRENIA

人的多巴胺D4受体在蛋白的第三个细胞质环中包含一个多态性。该基因具有不同数目的48个碱基重复序列。药理学研究表明，该受体是非典型的抗精神病药物氯氮平发挥抗精神病作用的部位，一些多态变体表现出不同的药理特性。1995年，我们建立了一种简便的聚合酶链式反应检测DRD4基因多态性的方法。我们从全血中提取基因组DNA并进行聚合酶链式反应分析。我们检测了两组无关精神分裂症患者和52名健康对照的D4等位基因频率。一组(B组)包括55例有其他精神分裂症家族成员的精神分裂症患者。另一组(B组)由47名精神分裂症患者…组成B组与对照组等位基因分布差异有统计学意义，B组4、5、6次重复等位基因频率显著增加，2次重复等位基因频率降低，B组与对照组等位基因分布有统计学差异。B组4次重复等位基因频率显著增加，与B组比较，差异有统计学意义。在本研究中，DRD4等位基因可能与有家族倾向的精神分裂症有关，也可能与无家族倾向的精神分裂症有关。虽然Nanko S.(1993)和Sommmer S.(1993)的研究表明DRD4等位基因与精神分裂症的关联不太可能，但我们的研究结果表明该基因多态与精神分裂症的关系还需要进一步的研究。较少

The human dopamine D4 receptor contains a polymorphism within the putative third cytoplasmic loop of the protein. The polymorphism is characterized by a varying number of 48-bp repeats in the gene.Pharmacological characterization has suggested that this receptor is the site through which the atypical neuroleptic clozapine exerts its antipsychotic action and that some polymorphic variants display different pharmacological properties. This polymorphism could underlie indivisual differences in susceptability to schizophrenia.In 1995, we have developed a simple method to detect DRD4 polymorphism by polymerase chain reaction.Genomic DNA was isolated from whole blood and analyzed by PCR.We have examined two groups of unrelated schizophrenic cases and 52 healthy controls to determine the frequency of different D4 alleles in these groups. One group (B+group) consisted of 55 schizophrenic cases who have other family members of schizophrenia. The other group (B-group) consisted of 47 schizophren … More ic cases who have no other family members of schizophrenia.Statistically significant difference in the distribution of the alleles existed between the cases of B+group and controls.The frequencies of the alleles of the 4,5 and 6 fold repeats significantly increased in the B+group, and the frequency of the alleles of 2 fold repeat decreased in the B+group.We also found statistically significant difference in the distribution of the alleles between the cases of B-group and controls. The frequency of the alleles of the 4 fold repeat significantly increased in the B-group.When we compare the allelic distribution in the B+group to that in the B-group, we found statistically significant difference. The frequency of the alleles of the 5 fold repeat significantly increased in the B+group.In our investigation possible associations were noted between the DRD4 alleles and schizophrenia with familial predispositions and also between the DRD4 alleles and schizophrenia without familial predispositions. Although the studies of Nanko S.(1993) and of Sommmer S.(1993) reported that the association between the DRD4 alleles and schizophrenia was unlikely, the result of our study indicates furtherinvestigaions on the relation between this polymorphism and schizophrenia are needed. Less