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Association Of Interation Among GR Gene, β2 -AR Gene And Occupational Stress With Essential Hypertension

Posted on:2012-12-24Degree:MasterType:Thesis
Country:ChinaCandidate:H ZhouFull Text:PDF
GTID:2154330335977006Subject:Occupational and Environmental Health
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[Objective]1. To investigate the the relationship between polymorphisms of GR gene in the HPA axis and occupational stress with EH among the traffic officers.2. To study the association of the polymorphisms of GR,β2-AR and their gene-gene interaction with EH among the traffic officers so as to elucidate the risky factors and mechanism of EH from the genetic point of view.3. To research the association of the polymorphisms of GR,β2-AR gene in the HPA axis and occupational stress with EH ,to clarify the association of the genetic and occupational stress with EH and the pathogenesis of EH in the high occupational stress.[Methods]1. Collected 730 traffic officers incluing train marshals, drivers, attendants by Cluster sampling from a railway branch men who Seniority more than 3 years. A total of 196 patients and 196 controls which were chosen in terms with age, job-matching among traffic officers. The OSI-R, SDS, Type A Behavior scales were adopted to evaluate the occupational stress, depressive symptom, type A behavior and other risky factors such as blood fat , blood glucose of each object, Analysis the relationship between these factors and EH.2. Desinging molecular epidemiology study , The genomic DNA was extracted from the sample blood , afterwards, the polymorphisms of GR,β2-AR were tested by PCR-RFLP.Haplotype frequencies and effects were computed by Haplo.stats,Analyze the role of gene, gene-gene interaction,gene-stress interaction on EH by GMDR software and multiple factor logistic regression model ,calculate the odds ratios and 95% confidence intervals.[Results]1. The odds ratios(OR) and 95% confidence intervals(95%CI) of GR Bcl? G/G and G/C were2.270(95%CI:1.048~4.919))and 1.599(95%CI:1.045~2.448).the polymorphisms of GR Bcl? gene may increase the risk of EH and the polymorphisms of GR G678S gene may not. Haplotype frequencies analysis revealed that not increased risk of EH with Hap3-GC,OR was 1.9785(95%CI:0.9326 ~3.2532).2. The average scores of occupational stress, stress reaction,A-type behavior in case group were higher in case than they in control group.There were statistically significant (P <0.05),The OR of them were 1.914,1.659,1.809.Compare the average scores of occupational stress among groups of different blood pressure levels showed that the scores of occupational stress,stress reaction in group of moderate to severe hypertension in occupational are higher than groups of mild hypertension and normal blood pressure;the score of A Type A behavior the group of mild hypertension was the highest,the followed is the group of severe hypertension group of normal blood pressure was lowest, There were different between th highest and the lowest(P <0.05).3. The stress-gene interaction GMDR model of EH showed the Type A behavior had the main effect; stress-gene interaction was exist in GR Bcl?,GR G678S, occupational stress, and Type A behavior.The OR of been exposed on had the mutational genetype of GR Bcl? and high occupational stresswere2.764(95%CI:1.392~5.489),3.491(95%CI:1.635~7.454),1.976(95%CI:1.025~3.810). The OR of been exposed on high occupational stress while had the wild genetype of GR G678S was 2.253(95%CI:1.070~4.744),suggest that stress-gene interaction was exist in GR G678S and occupational stress.4. The OR of been exposed on overweight while had the mutational genetype of GR Bcl?,GR G678S were 3.819(95%CI:2.100~6.946),2.287(95%CI:1.033~5.729).When the occupational stress act on them,the OR were (95%CI:2.289~17.066) and 3.379(95%CI:1.052~10.851),it more risky to EH than interaction between two or alone,suggest that there were interaction among GR gene, BMI and occupational stress.The OR of been exposed on diabetes,high lipids while had the mutational genetype of GR Bcl? were4.324(95%CI:0.821~22.606),2.147(95%CI:1.107~3.096),there were interaction among GR G678S gene and diabetes,The OR was 4.985(95%CI:1.552~16.009),there were interaction among GR G678S gene and diabetes,The interaction between GR and BMI,diabetes,high lipids, BMI is the strongest.5. The gene-gene interaction GMDR model of EH showed that gene-gene interaction was exist in GR Bcl?,GRG678S andβ2-AR Gln27Glu.After adjusting the confounding factors,The OR of been exposed on the mutational genetype of GR Bcl? while had the mutational genetype ofβ2-AR Gln27Glu,β2-AR Arg16Gly were 2.054(95%CI:1.06~3.954) and2.190(95%CI:1.06~4.339).there were interaction among GR Bcl? gene andβ2-AR Gln27Glu, β2-AR Arg16Gly.The OR of been exposed on the wild genetype GR G678S while had the mutational genetype ofβ2-AR Gln27Glu,β2-AR Arg16Gly were 2.604(95%CI:1.098~6.177) and 1.265(95%CI:0.475~3.367),there were interaction among GR G678S gene andβ2-AR Gln27Glu.6. The OR of been exposed on the mutational genetype of GR Bcl?,β2-AR Gln27Glu and occupational stress was 13.632(95%CI:1.613~115.226),it more risky to EH than interaction between two or alone,suggest that interaction was exist in three facts;The OR of been exposed on the mutational genetype of GR Bcl?,β2-AR Arg16Gly and occupational stress was 3.555(95%CI:1.280~9.870),the interaction in three fact was weak. The OR of been exposed on the mutational genetype ofβ2-AR Gln27Glu,β2-AR Arg16Gly,the wild genetype of GR G678S and occupational stress were 3.942(95%CI:1.081~14.374) and 1.579(95%CI:0.516~4.834),suggest that interaction was exist in GR G678S,β2-AR Gln27Glu and occupational stress.[Conclusions]1. EH among the traffic officers was associated with the Bcl? glucocorticoid receptor.2. The occupational stress will increase the risk of EH,the response to stress can explain the level of stress better and A-type behavior is a risk factor of EH.3. There were interactions between occupational stress and GR Bcl?,GR G678S gene of HPA axis and the interaction of GR G678S was weak, it educed that when occupational stress effect on body,GC in HPA axis can impact on hypertension by the GR gene.4. Under the action of occupational stress,the GR Bcl?, GRG678S gene in HPA axis can impact on hypertension by BMI and blood glucose which are important risk factors of EH.5. There were gene-gene interactions between GR Bcl?,GR G678S gene of HPA axis and Gln27Glu beta2-adrenergic receptor, which showed the additive effect like codominance mini-effect;By the action of occupational stress, the GC in HPA axis can impact on hypertension by the GR gene andβ2-AR gene.
Keywords/Search Tags:Essential hypertension, Glucocorticoid receptor, Beta-2 adrenergic receptor, Single nucleotide polymorphism, Occupational stress, Gene-gene interaction, Stress-gene interaction
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