| Background:Depression is the most common mood disorder,the prevalence of depression is up to 15~17%,and has been increasing year by year,but its etiology have not yet been elucidated.In recent years,a large number of studies have demonstrated that adult hippocampal neurogenesis is closely related to the occurrence of depression.CX3CL1 is an important member of the chemotactic cytokine superfamily and plays an important role in adult hippocampal neurogenesis.In addition,the CX3CL1 gene polymorphism can cause changes in its protein expression and is associated with the occurrence of a variety of diseases.The aim of this study was to investigate the relationship between the CX3CL1 gene rs170364 and rs614230polymorphism and the occurrence of depression in the Chinese Han population as well as its possible mechanisms,so as to provide a scientific basis for large-scale clinical screening of high-risk population with depression.Methods:A total of 1006 Chinese Han subjects were recruited in this case-control study,including 502 patients with depression and 504 healthy controls which matched for gender and age.All subjects were recruited from the Guangzhou Brain Hospital.Whole blood,serum samples and clinical data of all subjects were collected.High-throughput sequencing technology was used to detect the distribution of genotypes and alleles in the CX3CL1 gene rs170364,rs614230 locus.The expression of CX3CL1 in serum of the two groups was detected by enzyme-linked immunosorbent assay(ELISA).The effect of rs170364 polymorphism on the CX3CL1 gene transcription was explored by constructing rs170364 wild-type and mutant-type reporter gene vectors and transfecting into SH-SY5Y cells.All data were processed using SPSS 16.0statistical software.Results:The frequencies of T allele(OR=0.778,95%CI=0.633-0.955,p=0.016)and GT+TT genotype(OR=0.751,95%CI=0.585-0.965,p=0.025)of rs170364 in the CX3CL1 gene of depressive patients was significantly lower than that of the control group,suggesting that rs170364 mutation has a protective effect on depression.Further stratified analysis by gender showed that different frequencies of the CX3CL1 gene rs170364 mutation between depressive patients and healthy controls was mainly in female population(allele model,p=0.010;dominant genetic model,p=0.033;recessive genetic model,p=0.030),and rs170364 polymorphism plays a protective role in depression;but there was no significant difference in male population between the two groups(p>0.05).The allele and genotype frequencies of rs614230 in the CX3CL1 gene had no significant difference between depression group and the control group(p>0.05).The CX3CL1 gene rs170364 and rs614230 were moderate linkage disequilibrium in both depression group(D'=0.991,r~2=0.469)and the control group(D'=0.993,r~2=0.546).The haplotype analysis of rs170364-rs614230 showed that the frequency of TC haplotype in depressive patients was significantly lower than that in the control group(p=0.016,OR=0.777,95%CI=0.632-0.954),suggesting that carrying TC haplotype can reduce the risk of depression.ELISA detection showed that the level of CX3CL1 in serum of depression group was lower than that of the control group(5.992±5.427 ng/mL in the depression group;8.260±7.596 ng/mL in the control group),but there was no significant difference between the two groups(p=0.074).After the constructed CX3CL1 rs170364(G/T)reporter gene plasmid was transfected into SH-SY5Y cells,we found that the luciferase relative activity(RLA)after transfection of the rs170364-T reporter plasmid was significantly higher than the RLA after transfection of the rs170364-G reporter plasmid(p=0.004),which indicates that rs170364 mutation can enhance transcriptional activity of the CX3CL1 gene.Conclusions:The T allele and GT+TT genotypes of the CX3CL1 gene rs170364 locus in the Chinese Han population may be a protective factor for the occurrence of depression,especially in female population.Carrying the CX3CL1 gene T-rs170364-C-rs614230 haplotype may reduce the risk of depression.rs170364polymorphism can enhance transcriptional activity of the CX3CL1 gene. |
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