B-Adrenergic Receptor Polymorphisms, Occupational Mental Stress And Their Interaction Involved In The Pathogenesis Of EH In The High Risk Population

[Objective]1. To investigate the association of the polymorphisms ofβ1-AR,β2-AR,β3-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.2. To study the occupational mental stress and their environment-gene interaction withβ-AR polymorphisms involved in the pathogenesis of EH in the high risk population.[Methods]1. A case-control design was applied in association analysis ofβ-AR polymorphisms and EH sympathism. A total of 115 patients and 115 controls which were chosen in terms with age, job-matching among traffic officers. The OSI-R, STAI, SDS, Type A Behavior scales were adopted to evaluate the occupational stress, anxiety, depressive symptom, type A behavior and other risky factors such as blood fat , blood glucose of each object,as well as blood sample .The genomic DNA was extracted from the sample blood , afterwards, the polymorphisms of Arg389Glyβ1-AR,Gln27Gluβ2-AR,Trp64Argβ3-AR were tested by PCR-RFLP. Analyze the role of gene, gene-gene interaction on EH by MDR 1.1.0 software and multiple factor logistic regression model ,calculate the odds ratios and 95% confidence intervals.2. Using case-control study to analyze the causative agents in different risk population .Classify male marshals as high risk population while train crew as the lower risk population. we have identified 47 essential hypertension patients and 47 controls from marshals,68 patients and 136 controls from train crew. All the control subjects were frequency-matched to the cases on age(±3 years) ,job and gender. Analyze the role of environment-gene interaction on EH by MDR 1.1.0 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 Arg/Gly+Gly/Gly, Gln/Glu+Glu/Glu, Trp/Arg + Arg/Arg were 1.351(95%CI: 0.743~2.454), 2.266 (95%CI:1.132~4.536) and 1.985(95%CI:1.051~3.750);The OR of Gln27Glu beta2- adrenergic receptor polymorphisms was bigger than the two others;The MDR model show that beta2-adrenergic receptor polymorphisms had the main effect,which mean beta2-adrenergic receptor polymorphisms was a independent risk factor.2. The result of gene-gene interaction analysis by MDR model showed there was a gene-gene interaction among polymorphisms of Arg389Glyβ1-AR,Gln27Gluβ2-AR,Trp64Argβ3-AR, and the crossover analysis had confirmed this result.The OR of mutational genetype of Gln27Gluβ2-AR with Trp64Argβ3-AR was 5.32, which had the statistical significance.3. The odds ratios and 95% confidence intervals of occupational stress, stress reaction, type A behavior in high risk population were 2.659(95%CI:1.326-5.329), 5.386(95%CI:2.177-13.328) and 4.236(95%CI:1.471-12.199); The odds ratios and 95% confidence intervals of type A behavior and trait anxiety were 13.923(95%CI :8.771~29.248)and 6.847(95%CI :2.786~15.540) in low risk population.4. The environment-gene interaction MDR model of EH in high risk population showed the occupational stress had the main effect; environment-gene interaction was exist in Gln27Glu beta2-adrenergic receptor, occupational stress, trait anxiety and depressive symptom;The OR of been exposed on high occupational stress while had the mutational genetype of Arg389Glyβ1-AR,Gln27Gluβ2-AR,Trp64Argβ3-AR were 5.343, 3.093 and 4.501.5. The environment-gene interaction MDR model of EH in low risk population showed environment-gene interaction was exist in Gln27Glu beta2-adrenergic receptor, trait anxiety and type A behavior; The OR of been exposed on type A behavior while had the mutational genetype of Arg389Glyβ1-AR,Gln27Gluβ2-AR,Trp64Argβ3-AR were 18.818,28.748 and 36.487.[Conclusions]1. Frequencies of the genetype ofβ1-AR Gly389Arg,β2-AR Gln27Glu andβ3-ARTrp64Arg in our study were in Hardy-Weinberg equilibrium,which were close to the Frequencies of the genetype of Asia reported by other studies;2. EH among the traffic officers was associated with the Arg389Gly betal-adrenergic receptor, Gln27Glu beta2-adrenergic receptor, Trp64Arg betal-adrenergic receptor polymorphisms, among which Gln27Glu beta2-adrenergic receptor was the most important predisposing gene. The functional disorder of sympathetic nervous system was an important pathogenesy of EH.3. There was a gene-gene interaction between Arg389Gly betal-adrenergic receptor and Gln27Glu beta2-adrenergic receptor, which showed the additive effect like codominance mini-effect. The function change of related acceptor initiated the damp of vasodil ability, while the enhancement of contractibility, the flexibility of the vascular reactivity and the weakness of fat metabolism, which may be one mechanism of the gene-gene interaction.4. In the relation between high occupational mental stress and EH, the factors such as working features and environment influence the high occupational mental stress, its types as well as the risk of developing EH. The high occupational mental stress was an important pathogenesy of the high case-rate of EH among train officers; While the trait anxiety, state anxiety and type A behavior made it more risky to develop EH.5. The environment-gene interaction among beta-adrenergic receptor polymorphisms and of occupational mental stress were different between high and low risk population, and it educed a different effect on EH among different expose level of occupational mental stress.