Association Of Gene-gene,Gene-environment Interaction And Depression In Cav1.2 Signal Transduction Pathway

Background and PurposeThe etiology of depression is complex,and its mechanism is not entirely clear.The incidence of depression is not simply generated through the abnormal changes of neurotransmitter produced by intracellular signal transduction,but by the complex signal transduction in the cell.Previous studies have shown that CREB has a significant correlation with the pathogenesis of depression and the onset of antidepressants.At present,there are few studies focusing on the relationship between gene gene and gene environment interaction in Ca _V1.2-CAMKIV-CREB signaling pathway and depression.Therefore,the whole genome association analysis was used in our study,based on the depression related signaling pathway Ca _V1.2-Ca MKIV-CREB.This study is to explore the relationship between depression and the interaction of genetic and environmental factors.MethodsWe collected specimens of peripheral blood from Chinese Northern 590 depression and 587 controls.Snapshot technique was used to detect the genotype frequency and allele frequency of CACNA1C,CAMK,and CREB1 polymorphism in case group and control group.The negative life events score and childhood trauma were evaluated by Life Events Scale?LES?and the questionnaire of general situation.The genotype and haplotype distributions were analyzed by?²test,the interactions of gene-gene were analyzed by generalized multifactor dimensionality reduction?GMDR?,and the interactions of gene-environment were analyzed by Logistic regression.ResultsDifferences in rs1006737,rs7297582,rs899036 genotype frequencies were observed between patients and controls?P<0.05?.There were no significant association between rs2239073,rs4765937,rs2239015,rs4565905,rs10501943,rs10519765,rs10509643,rs2300763,rs2300777,rs2300782,rs10491335,rs11904814,rs6740584,rs2551941,rs2253206 and depression?P>0.05?.Further more there was no significant association between the haplotype distribution between and depression?P>0.05?.Gene-gene interaction models showed that the interaction model of rs1006737-rs7297582;rs1006737-rs7297582-rs4765937;rs1006737-rs7297582-rs4765937-rs899036;rs1006737-rs7297582-rs4765937-rs899036-rs10519765;rs1006737-rs7297582-rs4765937-rs2239073-rs4765937-rs899036;rs1006737-rs7297582-rs4765937-rs2239073-rs4765937-rs6740584;rs1006737-rs4765937-rs2239073-rs4765937-rs2239015-rs2300777-rs2551941;rs1006737rs7297582-rs4765937-rs2239073-rs4765937-rs2239015-rs899036-rs2300777-rs255194 with a cross validation consistency of 10,10,10,7,3,4,10 and 10 and prediction error of 0.2934,0.2620,0.2328,0.2135,0.1919,0.1532,0.1054 and 0.0768were statistically significant difference between patients and controls?P<0.05?.Logistic regression analysis showed that the interaction between 5-HT1AR rs6295G⁺,rs6311 T⁺,rs6313 T⁺or rs5443 T⁺and negative life events was associated with depression(OR⁺_rs6295G=1.911;OR⁺_rs6311T=7.170;OR⁺_rs6313T=5.557;OR⁺_rs5443T=1.957).In addition,the interaction between rs6295 G⁺,rs878567 T⁺,rs10042486 C⁺,rs6740584 C⁺,rs2551941 T⁺or rs2253206 A⁺and childhood trauma was associated with depression(OR⁺_rs6295G=15.563;OR⁺_rs878567T=12.428;OR⁺_rs10042486C=12.341;OR⁺_rs6740584C=5.995;OR⁺_rs2551941T=4.260;OR⁺_rs2253206A=3.793).ConclusionsCACNA1Crs1006737,rs7297582,CAMK4rs899036 were associated with depression.Moreover,the interaction of CACNA1C rs1006737-CACNA1C rs7297582;CACNA1C rs1006737-CACNA1C rs7297582-CACNA1C rs4765937;CACNA1C rs1006737-CACNA1C rs7297582-CACNA1C rs4765937-CAMKIV rs899036;CACNA1C rs1006737-CACNA1C rs7297582-CACNA1C rs4765937-CAMKIV rs899036-CAMKIV rs10519765;CACNA1C rs1006737-CACNA1C rs7297582-CACNA1C rs4765937-CAMKIV rs2239073-CACNA1C rs4765937-CAMKIV rs899036;CACNA1C rs1006737-CACNA1C rs7297582-CACNA1C rs4765937-CAMKIV rs2239073-CACNA1C rs4765937-CREB1rs6740584;CACNA1C rs1006737-CACNA1C rs4765937-CAMKIV rs2239073-rs4765937-CAMKIV rs2239015-CAMKIV rs2300777-CREB1 rs2551941;CACNA1C rs1006737CACNA1C rs7297582-CACNA1C rs4765937-CAMKIV rs2239073-CACNA1C rs4765937-CAMKIV rs2239015-CAMKIV rs899036-CAMKIV rs2300777-CREB1 rs255194 were related to depression.The interaction between rs1006737,rs4565905,rs72975827,rs10509643 and negative life events was associated with depression.In contrast,the interaction between rs2239073,rs4765937,rs2239015,rs10519765,rs10501943,rs899036,rs2300763,rs2300777,rs2300782,rs10491335,rs11904814,rs6740584,rs2551941,rs2253206 and negative life events was not associated with depression.