Interactions Between CREB1 And BDNF Genes And Recurrent Major Depressive Disorder

ObjectiveTo investigate whether CREB1 gene and BDNF gene interaction are associated with depressive disorder.Methods1.In case and control design,six tagSNPs of CREB1 and BDNF gene from 768 recurrent major depressive disorder patients and 511 healthy controls were detected by SNP Sequenom MassArray analysis.2.The generalized multifactor dimensionality reduction(GMDR)method was used to analyze the interaction between genetic polymorphisms and obtain the optimal model.Haploview4.2 software was used for Linkage disequilibrium analysis and haplotype analysis.And it was also used to test for H-W.SPSS17.0 software was used to compare the differences in the frequency distribution of the alleles and genotypes of the five SNPs,sex,age between recurrent major depressive disorder group and the healthy control group;Binary logistic regression analysis verify the optimal model obtained by GMDR analysis.3.The statistical power analysis for the total sample was determined by online software system(http://www.stat.ubc.ca/~rollin/stats/ssize/caco.html).P<0.05 was considered statistically significant.Results1.Comparison of general data between depression and control group and H-W test of 5 SNPsThere was no significant difference in sex and age between the depression group and the control group(P>0.05).The genotype frequencies of five tagSNPs(CREB1rs3770704,rs2551645,rs4675690,BDNFrs7124442,rs10835210)were in line with the HWE balance(P>0.05).In control group,the frequency of mutation allele C of CREB1 rs889895 was 0.2%.It was failed to find nature polymorphism.It was not included in the statistical analysis.In the total sample(n = 1279,including the depression group and the control group),the statistical power was 0.99.2.Comparison of the frequency distribution of 5 SNPs alleles and genotypes in depression group and control groupThere was no statistically difference evident in genotype and allele distribution frequencies of five SNPs(CREB1 rs4675690 etc)between the depression group and the control group(all P>0.05).3.Interaction analysis CREB1 gene and BDNF genesAfter adjusting the factors as sex and age,the GMDR analysis showed rs10835210 was the best model with p-value 0.0107 of the 1000-Permutation test.GMDR analysis did not reveal optimal two-,three-,four-,five-dimensional models with significant prediction accuracies(P > 0.05)for recurrent major depressive disorder.4.The correlation between three genotypes of rs10835210 and recurrent major depressive disorderBinary logistic regression analysis showed rs10835210 had a statistically significant effect on the risk of recurrent major depressive disorder,with the OR(95%CI)values as 0.772(0.608~0.980).5.BDNF gene polymorphism and CREB1 gene polymorphism linkage disequilibrium analysis and haplotype analysisThere is no linkage disequilibrium between BDNFrs7124442,rs10835210.In CREB1rs3770704,rs2551645,rs4675690,CREB1rs2551645 and rs4675690 in linkage disequilibrium.The D 'value between the two sites was 0.904,the r2 value was 0.664,in line with D'?0.9 and r2> 0.5.The haplotype analysis of the sliding window containing rs2551645 and rs4675690 showed that there was no haplotypes which was associated with depressive disorder,P > 0.05.Conclusions1.BDNF rs10835210 locus on 11 chromosome may be one of the biological markers of recurrent major depressive disorder.2.There is a linkage disequilibrium between the two sites,CREB1rs2551645,rs4675690;The haplotypes containing alleles of CREB1rs2551645,rs4675690 may not be associated with recurrent major depressive disorder.3.The frequency of the mutated allele C of CREB1 rs889895 locus on 2 chromosome in the Chinese Han population was 0.2%,CREB1 rs889895 may belong a small mutation gene locus.4.CREB1rs3770704,BDNFrs7124442 may not be associated with recurrent major depressive disorder.