CREB1和BDNF基因多态性交互作用与反复发作抑郁症的关联研究

Association study on interaction effects of CREB1 gene and BDNF gene polymorphisms and recurrent major depressive disorder

目的探讨环腺苷酸（CAMP）反应元件结合蛋白1（CREBl）基因多态性（rs889895，rs3770704，rs2551645，rs4675690）与脑源性神经营养因子（BDNF）基因多态性（rs7124442，rs10835210）交互作用是否与反复发作抑郁症有关。方法提取768例反复发作抑郁症患者（抑郁组）及511名健康对照者（对照组）DNA，通过质谱分析检测5个标签SNP（tagSNP）基因型，采用x。检验分析抑郁组和对照组的等位基因和基因型的频度分布差异，广义多因素降维法（GMDR）分析基因间的交互作用及二元Logistic回归分析基因型与患病风险的相关性。结果调整性别年龄后，GMDR分析发现一阶模型中rs10835210为最优模型，样本测试精确度为0．5319，交叉验证一致性为10／10，且对反复发作抑郁症的患病风险有统计学意义（P=0．0107），未发现二阶及以上模型中各SNP位点间的交互作用对反复发作抑郁症患病风险有统计学意义（P〉0．05）；二元Logistic回归分析最优模型，发现携带杂合子AC的个体较携带野生型纯合子CC个体发生反复发作抑郁症的风险降低（OR=0．772，95％CI=0．608～0．980，P=0．033）；未发现CREBlrs889895在中国汉族人群中的基因多态性。结论BDNFrs10835210可能是反复发作抑郁症的生物学标记位点之一。

Objective To investigate the interactions between cAMP-response element-binding pro- tein 1 （ CREB1 ） gene polymorphisms （ rs889895, rs3770704, rs2551645, rs4675690） and brain derived neuro- trophic factor（BDNF） gene polymorphisms （rs7124442,rs10835210） and the association with recurrent ma- jor depressive disorder. Methods The blood samples were taken from 768 recurrent major depressive disor- der patients and 511 healthy controls.The DNA was isolated fi＇om blood samples and was detected by SNP Se- quenom Mass Array analysis. Chi-square test was used to compare differences in the frequency distribution of alleles and genotype between depression and controls. The generalized multifactor dimensionality reduction （GMDR） method was used to analyze the gene-gene interaction.Binary logistic regression was used to verify the optimal model. Results After adjusting the factors of sex and age, the GMDR analysis showed rs10835210 was the optimal model.In this model,the testing balanced accuracy was 0.5319 and cross-valida- tion consistency value was 10/10.And rs10835210 had a statistically significant effect on the risk of recurrent major depressive disorder（P= 0.0107）.There was no significant gene-gene interaction of five tag SNPs on recurrent major depressive disorder（P〉0.05 ）.Binary logistic regression analysis showed the AC contributed to a significantly lower risk of recurrent major depressive disorder than did the CC （OR = 0.772,95% CI= 0.608- 0.980,P=0.033） .It was failed to find the genetic polymorphism of CREB1 rs889895. Conclusion BDNF rs10835210 may be one of the biological markers of recurrent major depressive disorder.