LINKAGESTUDIES ON FAMILIES WITH MULTIPLE MEMBERS OF SCHIZOPHRENIA

人类多巴胺D4受体在该蛋白的假定的第三细胞质环内含有多态性。多态性的特征是基因中有不同数量的48bp重复。药理学特征表明，该受体是非典型抗精神病药氯氮平发挥其抗精神病作用的部位，一些多态性变体显示出不同的药理学特性。这种多态性可能是精神分裂症易感性的个体差异的基础。1995年，我们开发了一种用聚合酶链反应检测DRD4多态性的简单方法。从全血中分离基因组DNA，进行PCR分析。我们已经检查两组无关的精神分裂症病例和52名健康对照来确定不同的D4等位基因的频率在这些组。一组（B+组）由55名有其他精神分裂症家庭成员的精神分裂症患者组成。另一组（b组）由47例精神分裂症患者组成。B+组病例与对照组等位基因分布差异有统计学意义。B+组4、5、6倍重复的等位基因频率显著增加，2倍重复的等位基因频率显著降低。我们还发现b组与对照组的等位基因分布有统计学差异。4倍重复等位基因的频率在b组显著增加。当我们比较B+组和B组的等位基因分布时，我们发现有统计学上的显著差异。5倍重复等位基因的频率在B+组显著增加。在我们的调查中，我们注意到DRD4等位基因与有家族性倾向的精神分裂症之间以及DRD4等位基因与无家族性倾向的精神分裂症之间可能存在关联。虽然Nanko S.（1993）和Sommmer S.（1993）的研究报道了DRD4等位基因与精神分裂症之间的关联不太可能，但我们的研究结果表明，需要进一步研究这种多态性与精神分裂症之间的关系。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