| Objective: Bronchial asthma is one of the common chronic diseases.In addition to causing physical discomfort,it often leads to anxiety and depression in patients,which seriously affects the control of asthma and the quality of life of patients,resulting in a vicious circle.In order to understand the molecular mechanism of asthma with depression from the perspective of genetics,this study investigated the association between depression-related gene polymorphisms and the risk of bronchial asthma with depression.Firstly,the incidence of bronchial asthma with depression and its influencing factors were studied to explore the relationship between bronchial asthma with depression and the control and quality of life of bronchial asthma.Secondly,based on the common sensitive neuro-immune network indicators of bronchial asthma and depression,the plasma levels of IL-17,TNF-a,IL-6 and 5-HT in each group were measured to explore the combined depression of bronchial asthma.The changes of common sensitive indices of depressive nerve-immune network and their correlation with the progress of depression were analyzed.Finally,84 SNP loci closely related to depression were screened to analyze their distribution differences between bronchial asthma,bronchial asthma with depression and healthy control group,and the correlation between these loci and bronchial asthma with depression was analyzed.Further genetic correlation study was carried out.To clarify whether there is a linkage between SNPs of the same gene,the haplotype of SNPs and the association between bronchial asthma and depression,and explore the possible mechanism of bronchial depression affecting the control of asthma and reducing the quality of life.Methods: 1)387 patients with bronchial asthma who met the inclusion criteria were investigated with general data and questionnaires.Logistic regression analysis was used to analyze the influencing factors of asthma with depression,and linear correlation analysis was used to analyze the correlation between SDS and ACT and AQLQ.;2)The expression levels of IL-17,TNF-alpha and IL-6 in plasma were detected by ELISA,and 5-HT in plasma was detected by high performance liquid chromatography(HPLC).The changes of common sensitivities of neuro-immune network in patients with bronchial asthma complicated with depression and their correlation with the progression of depression were analyzed;3)84 depression-related factors were identified by using UCSC genome browser and haploview 4.2 software.Gene loci.DNA was extracted by centrifugal column and genotype analysis of 84 depression-related gene loci was performed by Sequenom Mass ARRAY SNP.Chi-square test and logistic regression analysis were used to study the OR values and confidence intervals of SNPs under co-dominance,dominance and recessiveness genetic models.To assess its association with bronchial asthma with depression,further linkage analysis and haplotype correlation analysis were performed,and logistic regression analysis was used to assess the association between haplotype of linked SNP and asthma with depression.Results: 1)A total of 387 asthmatic patients who met the inclusion criteria were investigated in this study.The detection rate of depression was 62.5%.Univariate Logistic regression analysis showed that compared with simple asthmatic patients,asthmatic patients with depression had sex,age,education,marital status,whether to work,family monthly income,status of illness persistence,whether to use drugs or not,and whether to use drugs or not.Symptoms(cough,wheeze,nighttime breathlessness,chest tightness)had statistical differences(P<0.05);Logistic multiple regression model was used to analyze the results: mild persistence(OR=2.529,95%CI=1.379-4.640),moderate/severe persistence(OR=2.260,95%CI=1.124-4.543)and a history of treatment(OR=2.461,95%CI=1.543 compared with untreated drugs).95%CI=1.388-4.366)is a risk factor for depression in asthmatic patients.Linear correlation analysis showed that with the increase of SDS score,the total AQLQ score gradually decreased,showing a negative linear correlation(P=0.000,r=-0.527).With the increase of SDS score,ACT score decreased gradually,showing a linear negative correlation(P=0.000,r=-0.533);2)Compared with the healthy control group,there was no significant difference in serotonin between asthma patients with mild depression(P>0.05),bronchial asthma patients with moderate depression had significant difference in serotonin(Z=-3.79,P<0.05),bronchial asthma patients with severe depression had significant difference in serotonin(Z=-2.172,P<0.05);bronchial asthma patients with mild depression and bronchial asthma patients with mild depression had significant difference(Z=-2.172,P<0.There was significant difference in serotonin between asthma with moderate depression(Z=-2.883,P < 0.05),and bronchial asthma with severe depression(Z=-2.587,P<0.05).There was no significant difference in serotonin between bronchial asthma with moderate depression and bronchial asthma with severe depression(P>0.05).The levels of IL-17 in asthma patients with mild depression were significantly different from those in healthy control group(Z=-4.95,P<0.05),bronchial asthma patients with moderate depression were significantly different(Z=-4.79,P < 0.05),bronchial asthma patients with severe depression were significantly different(Z=-4.03,P<0.05);bronchial asthma patients with mild depression and bronchial asthma patients with moderate depression were significantly different(Z=-4.03,P<0.05).There was significant difference in IL-17 level between severe depression and bronchial asthma(Z=-2.01,P<0.05).There was significant difference in IL-17 level between bronchial asthma with moderate depression and bronchial asthma with severe depression(Z=-2.55,P<0.05).There was significant difference in IL-17 level between bronchial asthma with moderate depression and bronchial asthma with severe depression(Z=-2.46,P<0.05).There were significant differences in asthma levels,but there were also significant differences between asthma patients with different degrees of depression.The level of IL-6 in asthma patients with mild depression was significantly different from that in healthy control group(Z=-7.15,P<0.05).The level of IL-6 in asthma patients with moderate depression was significantly different(Z=-5.81,P<0.05);the level of IL-6 in asthma patients with severe depression was significantly different(Z=-4.17,P<0.05);the level of IL-6 in asthma patients with mild depression was significantly different(Z=-4.17,P<0.05).Compared with bronchial asthma with moderate depression,there was no significant difference in IL-6 level(P>0.05).There was no significant difference in IL-6 level between bronchial asthma with moderate depression and bronchial asthma with severe depression(P>0.05).There was no significant difference in IL-6 level between healthy control group and bronchial asthma with depression group(P>0.05).There was no significant difference between asthma group and depression group.The level of TNF-alpha in asthma patients with mild depression was significantly different from that in healthy control group(Z=-5.53,P<0.05).The level of TNF-alpha in asthma patients with moderate depression was significantly different(Z=-3.68,P < 0.05);the level of TNF-alpha in asthma patients with severe depression was significantly different(Z=-2.34,P < 0.05);the level of TNF-alpha in asthma patients with mild depression was significantly different(Z=-2.34,P < 0.05).There was no significant difference in TNF-alpha level between depression and bronchial asthma with moderate depression(P>0.05),and between bronchial asthma with severe depression(P>0.05).There was no significant difference in TNF-alpha level between bronchial asthma with moderate depression and bronchial asthma with severe depression(P>0.05).Compared with TNF-a level,there was a significant difference(P<0.05),but there was no significant difference between asthma with different degrees of depression group(P>0.05);3)Analysis of genotypes and allele frequencies among healthy control group,simple asthma group,simple asthma group and asthma group with depression showed that there was at least one significant chi-square difference in the distribution of 18 loci in co-dominant,dominant,recessive models or alleles.Logistic analysis of depression-related SNP genotypes and asthma status revealed that 21 of 84 loci had at least a regression relationship.When we observed the linkage status of 84 loci in asthmatic patients,we found that 16 pairs of SNPs were highly linked to form haploid.Compared with healthy control group,4 haploid types of three genes were significantly associated with asthmatic status,namely,GRPHN gene rs10129827,rs28762177 GG(OR=1.258,P=0.02582),BDFN gene rs6265,rs204904 6 CA.Type(OR=1.267,P=0.0176),TT(OR=0.763,P=0.008),HTR1 A rs878567,rs6295 TT(OR=1.28,P=0.030).Conclusion: 1)Bronchial asthma patients are prone to depression,depression is a common concomitant disease of bronchial asthma,which is affected by many factors,and depression significantly affects the disease control and quality of life of bronchial asthma;2)It was found that the levels of IL-17,IL-6,TNF-alpha and 5-HT were closely related to the occurrence of depression in patients with bronchial asthma,among which IL-17 and 5-HT were closely related to the development and severity of depression in patients with bronchial asthma,suggesting that the neuroimmune network of patients with bronchial asthma and depression might be in disorder;and these four indicators might be used to diagnose the occurrence of depression in patients with AST Potential biomarkers for exhibition;3)The distribution of 84 gene loci related to depression was different among simple asthma,asthma with depression and healthy control group.It was found that some loci were significantly correlated with disease status,and there was strong interaction among loci to control the susceptibility of disease.The CA genotype of BDFN and GG genotype of GRPHN gene may be risk factors for asthma in depressive patients,while TT genotype of BDFN gene and TT genotype of HTR1 A gene may be protective factors for asthma in depressive patients.Three sites of rs1800044(HT1RA),rs12520799(DNA NP1),rs6265(BDNF)in depressive patients with asthma or asthma with depression may cause heteronymous mutations.HT1 RA and BDNF genes are receptors and regulators of inflammatory cytokines respectively.Heteronymous mutations may lead to imbalance of inflammatory cytokine levels and activities,which may lead to some molecular mechanisms of asthma and depression.Studies have shown that rs1800044(HT1RA),rs12520799(DNA NP1),rs6265(BDNF)may be the important genetic basis of bronchial asthma with depression.The results provide a basis for further understanding of asthma with depression and its pathogenesis,early screening,early prevention and early diagnosis of molecular genetics. |
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