BDNF基因多态性与内化性精神障碍的关联研究

摘要

目的 探讨脑源性神经营养因子(BDNF)基因多态性与内化性精神障碍之间的关联.方法 采用多重聚合酶链反应(PCR)和连接酶检测(LDR)的方法,对259例诊断为内化性精神障碍大学生和269名健康大学生BDNF基因上的3个tag SNPs位点进行基因型检测,对结果进行单倍型分析和多位点联合分析.结果 各位点在病例组和对照组中的基因型分布均符合Hardy-Weinberg平衡.rs12273539位点在病例和对照组中的基因型和等位基因的频数分布差异均无统计学意义(P值均＞0.05).rs10835210和rs2030324位点在病例和对照组中的基因型和等位基因的频数分布差异均有统计学意义(P值均＜0.05).病例组中rs10835210的A等位基因和rs2030324的C等位基因频率明显高于对照组,携带有rs10835210的A等位基因和rs2030324的C等位基因是内化性精神障碍发生的危险因素(OR=1.877,P＜0.001;OR=1.347,P＜0.05).多位点联合作用分析显示,这3个位点的联合作用与内化性精神障碍相关联(χ~2=23.537,P＜0.001).结论 BDNF基因可能是引起内化性精神障碍发病的易感基因.%Objective To investigate the genetic association between brain-derived neurotrophic factor(BDNF)gene polymorphism and internalizing disorders,to provide the theoretical basis to explore the etiology of internalizing disorders.Methods PCR-based ligase detection reaction(PCR-LDR)was applied to tag single nucleotide lengh polymorphism(SNPs)of BDNF gene among 259 undergraduates affected by internalizing disorders and 269 healthy undergraduates.Haplotype analysis and multiple locus analysis were conducted to analyze the genotyping data.Results The genotypic frequency of tag SNPs of BDNF gene did not deviate from Hardy-Weinberg equilibrium in both case and control groups.Rsl2273539 was not associated with internalizing disorders(P＞0.05),but rs10835210 and rs2030324 were related to internalizing disorders(P＜0.05).The case group had more A allele of rs10835210 and C allele of rs2030324 when compared to the controls while A allele of rs 10835210 and C allele of rs2030324 seemed to be the risk factors of internalizing disorder(OR=1.877,P＜0.001;OR=1.347,P＜0.05).Results of multiple locus analysis showed that the haplotype composed by the three tag SNPs which was related to internalizing disorders(χ~2=23.537,P＜0.001).Conclusion BDNF gene might serve as the susceptible gene for internalizing disorder.