精神分裂症与多巴胺D4受体基因多态性的关联分析

目的：在中国汉族人群中寻找散发精神分裂症与多巴胺D4受体（DRD4）基因第3外显子48bp片段可变数串联重复（VNTR）多态性的关系。方法：使用病例－对照的关联分析的方法。对符合诊断标准的510名精神分裂症患者／171名正常对照就DRD4基因第三外显子48bp VNTR的多态性进行检测并进行关联分析。结果（1）所检测人群48bp VNTR多态性表现国2－7次重复，4次重复的等位基因在精神分裂症患者及对照组中分别占78．6％及76．9％，2次重复分别占16．2％及19．3％；（2）精神分裂症患者与正常对照之间的基因型频率分布差异具有显著意义，病例组短重复序列的基因型（2／2，2／3）频率（3．3％）显著低于对照组（10．5％）（X^2=14．88，df=2,P=0.00)；（3）病例组含4次重复的基因型比例（95．9％）显著高于对照组（88．3％）（X^2＝13．00,df＝1,P=0.000)。结论：中国精神分裂症人群DRD4基因第三外显子48bp VNTR多态性主要集中于4次重复片段，48bp的重复次数可能与精神分裂症相关，短重复序列减少或含4次重复的基因型增多可能增加对精神分裂症的易感性。

Schizophrenia and dopamine D4 gene polymorphism in Chinese population: association analysis

OBJECTIVE: To investigate the association of the 48 bp variable number tandem repeat (VNTR) polymorphism in the dopamine D4 receptor (DRD4) gene exon III with schizophrenia in Chinese Han population. METHODS: Case-control association study was adopted to analyze the association between the 48 bp VNTR polymorphism of DRD4 gene exon III in 510 DSM-IV schizophrenics and 171 psychiatrically normal controls. RESULTS: (1) The DRD4 gene 48 bp VNTR polymorphism was manifested as 2-7 repeats, with the 4 repeats the most common (78.6% in schizophrenics and 76.9% in controls respectively). The frequency of 2 repeats was 16.2% and 19.3% in the schizophrenics and controls respectively. (2) The genotypic frequency was statistically significantly different between the schizophrenics and the controls. The genotypic frequency of short tandem repeats (2/2 and 2/3 genotype) was lower in patients (3.3%) than in controls (10.5%) (chi 2 = 14.88, df = 2, P = 0.00). (3) the frequency of the genotype with 4-repeat allele in patients was higher (95.9%) than in controls (88.3%) (chi 2 = 13.00, df = 1, P = 0.000). CONCLUSION: The most common allele in Chinese schizophrenics was 4 repeats in the 48 bp VNTR polymorphism of DRD4 gene exon III. The repeat number of 48 bp is probably associated with schizophrenia. Lack of 2-3 repeats or excess of genotype with 4-repeat allele may be associated with increased vulnerability to schizophrenia.