摘要目的 探讨色氨酸羟化酶 2 ( TPH2 )单核苷酸多态性( rs4570625、 rs11178997、rs120074175)与负性生活事件交互作用与抑郁症患病的关联.方法 提取中国北方地区300例抑郁症患者(病例组)和300名健康对照者(对照组)基因组DNA,采用 PCR技术扩增DNA片段,检测病例组及对照组的基因型.应用生活事件量表对病例组和对照组进行问卷调查.采用χ2检验分析抑郁组和对照组的等位基因和基因型的频率分布差异,广义多因素降维法( GMDR)分析基因和环境的交互作用及二元 Logistic回归分析SNP位点和负性生活事件对患病风险的预测.结果 调整性别和年龄后,GMDR分析发现四阶模型rs4570625、rs11178997、rs120074175与负性生活事件为最优模型,样本测试精确度为0.7838,交叉验证一致性为10/10,且对抑郁症的患病风险有统计学意义( P＝0.001);二元Logistic回归分析最优模型,发现带有rs11178997 A+等位基因(AA,AT)和rs120074175 A+等位基因(AA,AG)的个体,有负性生活事件时OR值分别为24.307(95%CI＝13.007～45.427)和38.250(95%CI＝21.148～69.181),显示出了较高的抑郁症患病风险.结论 TPH2基因(rs11178997、rs120074175)、负性生活事件的交互作用与抑郁症患病存在一定联系.

abstractsObjective To verify the interaction between single nucleotide polymorphism of trypto-phan hydroxylase 2 (TPH2) (rs4570625,rs11178997,rs120074175) and negative life events and the asso-ciation with major depressive disorder (MDD) in a Chinese population.Methods Totally 300 cases of pa-tients with major depressive disorder and 300 healthy controls in northern China were enrolled and the ge-nomic DNA were extracted. PCR was used to detect the polymorphisms of rs4570625, rs11178997, rs120074175.Questionnaire survey was conducted on the case group and the control group.Chi-square test was used to compare the differences in the frequency distribution of alleles and genotype between two groups. The generalized multifactor dimensionality reduction ( GMDR) method was used to analyze the interaction between gene and environment.Binary logistic regression was used to verify the optimal model.Results After adjusting the factors of sex and age,the GMDR analysis showed rs4570625,rs11178997,rs120074175 and negative life events were the optimal model.In this model, the testing balanced accuracy was 0.7838 and cross-validation consistency value was 10/10.There was statistically significant effect on the risk of major de-pressive disorder ( P ＝ 0.001 ). Binary logistic regression analysis showed that individuals, who had rs11178997 A+ genotype (AA,AT),rs120074175 A+genotype (AA,AG) and negative life events,had sig-nificant OR values of 24.307(95%CI＝13.007-45.427) and 38.2502(95%CI＝1.148-69.181),showing a higher risk of depression.Conclusion The interaction between TPH2 gene (rs11178997,rs120074175) and negative life events plays an important role in depression.