精神分裂症与多巴胺D4基因和5-羟色胺2A受体基因的关联分析

Association analysis between the dopamine D4 receptor gene and the 5-HT2A receptor gene and schizophrenia in Chinese

目的探讨湖南地区汉族人群多巴胺D4受体（DRD4）基因和5-羟色胺2A（5-HT2A）受体基因与精神分裂症遗传易感性的关系及其相互作用对精神分裂症的影响。方法81例精神分裂症患者单一用氯氮平治疗6—8周，利用阳性与阴性症状量表（PANSS）评定氯氮平的疗效，并根据量表的减分率将患者分为有效和无效两组。采用聚合酶链式反应（PCR）及限制性片段长度多态性（RFLP）技术检测患者组和对照组DRIM基因48bp可变串联重复（VNTR）多态性及5-HT2A受体基因T102C多态性的基因型及等位基因的频率。结果有效组患者DRIM＊3／5基因型（DRIM＊3／5）频率（40．3％）明显高于对照组（23．9％）。DRIM＊3等位基因携带者中，精神分裂症5-HT2A受体基因的A2等位基因频率（50．0％）显著高于对照组（30．0％）；非DRD4＊5／5携带者中，精神分裂症5-HT2A受体基因的A2／A2基因型（22．0％）及A2等位基因频率（48．8％）显著高于对照组（5．0％；32．5％）。结论DRD4基因48bpVNTR多态性可能与精神分裂症的某些亚型（对氯氮平有效者）遗传易感性相关。DRD4基因和5-HT2A受体基因可能存在交互作用，DRD4＊非5／5基因型及携带DRIM＊3等位基因者可能影响5-HT2A受体基因A2等位基因及A2／A2基因型与精神分裂症关系。

Objective To investigate the relationship between the dopamine D4 receptor （DRD4） gene and 5-HT2A receptor gene and the susceptibility of schizophrenia in Hunan Han population and explore the effect of interaction of the two genes on the presence of schizophrenia. Methods 81 patients with schizophrenia were treated by clozapine for 6 - 8 weeks. The clinical response was determined by the Positive and Negative Symptom Scale （PANSS）. The patients were divided into two groups according to the reductive rate of score of PANSS ≥ 50% and 〈50% respectively. Genotypes and alleles in these patients were examined with polymerase chain reaction （PCR） and restriction fragment length polymorphism （RFLP） technique. Results The frequency of the genotype of DRD4 ＊ 3/5 was significantly more prevalent in response group （40.3%）than in control group （23.9%）. In the carrier without DRD4 ＊ 5/5, the frequency of A2/A2 genotype（22.0% ） and A2 allele（48.8% ） was more higher in schizophrenia group than in control group（ 5.0% ,32.5% ）. In the carrier with DRD4 ＊ 3, the frequency of A2 allele （50.0%） was significantly more prevalent in schizophrenia group than in control group（ 30.0% ）. Conclusion DRD4 gene 48bp VNTR polymorphism may affect the susceptibility of some subtype （response to clozapine） of schizophrenia. The result might exhibit an interaction of two genes on schizophrenia . While the relation of schizophrenia to A2/A2 genotype and A2 allele might be subject to the genotype without DRD4 ＊ 5/5 or DRD4 ＊ 3.