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

Abstract

Objective To investigate the interactions between cAMP-response element-binding protein 1(CREB1)gene polymorphisms (rs889895, rs3770704, rs2551645, rs4675690)and brain derived neurotrophic factor(BDNF)gene polymorphisms (rs7124442, rs10835210) and the association with recurrent major depressive disorder. Methods The blood samples were taken from 768 recurrent major depressive disorder patients and 511 healthy controls.The DNA was isolated from blood samples and was detected by SNP Sequenom 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-validation 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. Key words: Recurrent major depressive disorder; cAMP-response element binding protein; BDNF; Tag SNP; Generalized multifactor dimensionality reduction