摘要
目的 探讨多巴胺D2 受体基因启动子 (DRD2P)、5 羟色胺 2A受体基因 (5 HT2A)、儿茶酚氧位甲基转移酶基因 (COMT)和单胺氧化酶A(MAO A)基因相应多态性与汉族精神分裂症的关系及遗传学特征。方法 纳入至少有 2名同胞符合国际疾病分类第 10版的精神分裂症诊断标准、父母存活的核心家系 43个 ,完成由哈佛大学提供的遗传学研究用诊断性检查和遗传学研究用家属会谈表 ,同时采集静脉血 10ml,提取DNA。用聚合酶链反应 (PCR)对候选基因片段进行扩增 ,酶切后用琼脂糖凝胶电泳检测基因型。统计分析方法采用 χ2 检验、相关分析及传递不平衡检验 (TDT)等。结果(1)DRD2P、5 HT2A、COMT的基因型和等位基因频率在患病同胞组、非患病同胞组和父母组之间的分布差异无显著性 (P >0 0 5 )。MAO A多态性在父母组 (86名 )的 941T/ 941G和 941G/ 941G基因型频率与患病同胞组 (2 9例 )及非患病同胞组 (48名 )之间的差异有显著性 ,但非患病同胞组与患病同胞组之间的差异无显著性 (P <0 0 5 )。 (2 )在患病同胞中 ,MAO A的 941G等位基因传递较多 [(χ2 =5 33,P <0 0 5 ,比数比 (OR) =3 32 ,95 %可信区间 (95 %CI) =1 5 8～ 6 99) ];在非患病同胞中 ,DRD2P的- 2 41A等位基因 (χ2 =6 76 ,P <0 0 1,OR =3 17,95 %CI
Objects Polymorphism of genes for dopamine D 2 receptor promoter (DRD2P), 5 HT 2A receptor (5 HT 2A ), catechol o methyltransferase (COMT), and monoamine oxidase A type (MAO A) were examined synchronously for exploring the genetic factors related to schizophrenia Methods Forty three pedigrees with at least two siblings affected schizophrenia according to ICD 10 criteria and biological parents alive were recruited The Chinese versions of the Diagnosis interview for Genetics Study (DIGS) and the Family Interview for Genetics Study (FIGS) were fulfilled Genomic DNA was isolated from lymphocytes by a standard procedure After polymerase chain reaction (PCR), the cleavage was done Then the genotypes were read by 1% agarose gel electrophoresis with 100 bp DNA ladder The chi square test, correlation analyses, and the transmission disequilibrium test (TDT) were employed Results (1) No significantly different distribution between groups of parents, non affected siblings and affected siblings was found, when polymorphism of DRD2P, 5 HT 2A , and COMT were analyzed But significantly different distribution of genotype or allele was found, when comparing with 941A/941G and 941G/941G genotypes of MAO A between groups of parents and non affected siblings, or parents and affected siblings No significant difference, however, was found between the groups of non affected siblings and affected siblings (2) 941G allele of MAO A was transmitted significantly more to affected siblings from parents (χ 2= 5 33, P <0 05, OR =3 32,95% CI : 1 58 6 99) And 941A allele of MAO A and -241A allele of gene for DRD2 promoter were transmitted significantly more to non affected siblings from parents (χ 2=4 84, P <0 05, OR =6 04, 95% CI : 2 01 18 69) But both T102G polymorphism of 5 HT 2A and Val108Met polymorphism of COMT were not found to have significant transmission disequilibrium ( P >0 05) (3) Significant relationship was found between genotype of gene for DRD2P promoter, or COMT, or MAO A and schizophrenic clinical features, but not genotype of T102C polymorphism of 5 HT 2A Conclusions (1) Our results support hypothesis of DA dysfunction in the etiology of schizophrenia (2) From this study, we infer that there are relationships between these candidate genes and schizophrenia at different degree That is MAO A>DRD2P>COMT>5 HT 2A .
出处
《中华精神科杂志》
CAS
CSCD
北大核心
2001年第2期90-93,共4页
Chinese Journal of Psychiatry
