精神分裂症患者脑源性神经营养因子与多巴胺D1受体基因交互作用研究

Gene-gene interaction between genes of brain-derived neurotrophic factor and dopamine Dl receptorin schizophrenia

目的探讨多巴胺D1受体（DRDl）与精神分裂症的关系是否与脑源性神经营养因子（BDNF）有关。方法选取BDNF基因Val66Met位点（rs6562）以及DRDl基因5个标签单核苷酸多态性（SNP）（rs4532、rs5326、rs2168631、rs6882300和rs267418），采用TaqMan探针SNP基因分型技术对340例精神分裂症患者（患者组）和375名健康对照者（对照组）进行检验，使用多因子降维法软件（MDR）分析基因-基因交互作用。结果以上6个SNP基因型及等位基因频率分布在患者组与对照组之间差异无统计学意义（P5〉0．0083）；MDR分析结果显示，BDNF与DRD1基因交互作用存在于两位点模型（rs6265-rs5326）[OR=1．83，95％可信区间（CI）：1．33～2．53；X2=13．91，P=0．0002]，t位点模型（rs6265-rs4532-rs6882300）（OR=2．06，95％CI：1．53～2．78；）（X2=22．73，P〈0．0001）及四位点模型（rs6265-rs5326-rs2168631-rs6882300）（OR=2．85，95％C／：2．09～3．89；X2=44．99，P〈0．0001）。结论精神分裂症患者BDNF与DRDl基因存在交互作用，DRDl在精神分裂症发生过程中的作用可能与BDNF有关。

Objective To explore the impact of brain-derlved ncurotrophic factor（BDNF） on the contribution of dopamine D1 receptor （DRD1） to schizophrenia. Methods One single nueleotide polymorphism （SNP） （ Va166Met, rs6562 ） within BDNF gene and five tag-SNPs （ rs4532, rs5326, rs2168631,rs6882300 and rs267418） within DRD1 gene were genotyped in 340 schizophrenic patients and 375 healthy controls. The gene-gene interaction between BDNF and DRD1 was analyzed by Multifactor Dimensionality Reduction （MDR） software. Results There were no significant differences on the frequencies of the genotypes and alleles of the six SNPs between patients and controls （P 〉 0. 0083）. MDR revealed that the significance were shown in patterns with 2 SNPs （rs6265-rs5326; OR = 1.83, 95% CI： 1.33 - 2.53, X2 = 13.91 , P = O. 0002 ） , 3 SNPs （ rs6265-rM532-rs6882300 ; OR = 2.06, 95 % CI： 1.53 - 2.78, X2 = 22.73, P 〈 0. 0001 ） and 4 SNPs （ rs6265-rs5326-rs2168631-rs6882300; OR = 2.85, 95% CI： 2.09- 3.89,X2 = 44.99, P 〈 0. 0001 ）. Conclusion There may be the gene-gene interaction between genes of BDNF and DRD1 in schizophrenic patients. BDNF may play an important role in the contribution of DRD1 to the development of schizophrenia.