Shaikh S, Collier D A, Sham P, Pilowsky L, Sharma T, Lin L K, Crocq M A, Gill M, Kerwin R
Department of Psychological Medicine, Institute of Psychiatry, London, United Kingdom.
Am J Med Genet. 1995 Dec 18;60(6):541-5. doi: 10.1002/ajmg.1320600611.
We have examined the hypothesis that a variable number of tandem repeats in the third cytoplasmic loop of the dopamine D4 receptor influences clinical response to clozapine using a sample of 189 schizophrenic patients. Alleles of the 48-bp repeat, which range from two to ten copies in the normal human population, were analysed by the polymerase chain reaction using genomic DNA as template. Association between these alleles and response to clozapine was tested using the difference in pre- and post-treatment GAS scores as a measure of response. We found no statistically significant variation between genotypic groups and response by analysis of variance. We conclude that the variation of the number of 48-bp repeats alone does not determine response to clozapine. Larger studies are underway to determine if there is a more subtle relationship with sequence variation within the repeats or at other polymorphic sites within the gene that may provide evidence for a component of clozapine's action being at D4 receptors.
我们使用189名精神分裂症患者的样本，检验了多巴胺D4受体第三细胞质环中串联重复序列数量可变会影响氯氮平临床反应这一假设。以基因组DNA为模板，通过聚合酶链反应分析了48碱基对重复序列的等位基因，其在正常人群中的拷贝数范围为2至10个。使用治疗前和治疗后总体评定量表（GAS）评分的差异作为反应指标，测试了这些等位基因与氯氮平反应之间的关联。通过方差分析，我们发现基因型组与反应之间没有统计学上的显著差异。我们得出结论，仅48碱基对重复序列数量的变化并不能决定对氯氮平的反应。正在进行更大规模的研究，以确定重复序列内或基因内其他多态性位点的序列变异是否存在更微妙的关系，这可能为氯氮平作用的一部分是通过D4受体提供证据。
