新疆油田工人ADD1、β2-AR基因和职业紧张交互作用与高血压患病的关系

Relationship of hypertension with interactions among ADD1 gene, β2-AR gene, and occupational stress in Xinjiang oilfield workers

[背景]目前,职业紧张与高血压的研究很多,但流行病调查研究难以说明二者之间的关系,高血压是由基因与环境共同作用的结果,虽然我国克拉玛依地区油田工人的职业紧张与高血压的关系调查已进行十年,但基因环境的深入研究较少。[目的]探讨新疆油田工人α-内收蛋白基因(ADD1)、β2肾上腺素受体基因(β2-AR)交互作用以及职业紧张与两基因交互作用对高血压的影响,从分子生物学的角度为防治高血压疾病提供新思路。[方法]选取352名新疆油田作业工人,在同一岗位工作时间一年以上者,无精神疾病家族史,愿意配合填写调查表的研究对象。利用职业紧张量表修订版进行职业紧张程度评价,按照年龄、性别特征进行1∶1匹配,病例组、对照组各为176人,利用聚合酶链式反应限制性片段长度多态性技术检测基因多态性。采用条件logistic回归对基因和高血压之间的关联性进行分析,采用广义多因子降维法(GMDR0.9)进行基因-基因、基因-环境交互作用的分析。采用MDR(3.0.2)软件绘制交互作用的树状图。[结果]油田工人病例组职业紧张得分高于对照组(P <0.05)。病例组与对照组的基因型分布分析显示:ADD1基因Gly460Trp位点、rs17833172位点在两组间差异有统计学意义(P <0.05),β2-AR基因1023位点、rs1042717位点在两组间差异无统计学意义(P> 0.05)。校正混杂因素后logistic回归分析显示:ADD1基因rs17833172位点GG基因型是高血压患病的危险因素(OR=2.948,95%CI:1.209~7.187,P <0.05),ADD1基因Gly460Trp位点TT基因型是高血压患病的保护因素(OR=0.35,95%CI:0.155~0.788),其余两个基因位点与高血压患病之间的关联差异无统计学意义(P> 0.05)。交互作用分析结果显示:ADD1 Gly460Trp、rs17833172,β2-AR rs1042717间的基因-基因交互模型为最优模型(P <0.05);职业紧张与Gly460Trp位点、rs17833172、1023位点、rs1042717位点的基因环境交互模型为最优模型(P <0.05)。树状图显示ADD1 Gly460Trp与β2-AR rs1042717位点间存在较强的正交互作用,职业紧张与4个单核苷酸多态性之间存在交互作用。[结论]ADD1基因rs17833172位点GG基因型是患高血压的危险因素,ADD1因基Gly460Trp位点TT基因型是高血压患病的保护因素。ADD1基因Gly460Trp位点与β2-AR基因rs1042717位点的正交互作用可能会增加油田工人高血压患病风险。ADD1基因Gly460Trp位点、rs17833172位点,β2-AR基因rs1042717位点、1023位点与职业紧张的交互作用与油田工人高血压的患病有关。

[Background] At present, there are many studies on occupational stress and hypertension, but epidemiological studies are difficult to explain the relationship between them. Hypertension has been recognized as the result of gene-environment interaction. Although studies on the relationship between occupational stress and hypertension have been carried out for about10 years in oilfield workers in Karamay of China, there are few in-depth studies on genetic environment.[Objective] This study is conducted to explore the effects of interaction between alpha-adducin(ADD1) gene and beta-2 adrenergic receptor(β2-AR) gene and the interaction between occupational stress and the two genes on hypertension in Xinjiang oilfield workers,and provide new molecular biological ideas for the prevention and treatment of hypertension.[Methods] A total of 352 Xinjiang oilfield workers were selected, who had worked in the same job for more than one year, had no family history of mental illness, and consented to complete a questionnaire. The occupational stress level was evaluated using the revised version of Occupational Stress Scale. There were 176 cases and 176 controls after being matched by age and gender in a 1 : 1 ratio. The gene polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism technique. Conditional logistic regression was used to analyze the association between genes and hypertension, and generalized multi-factor dimensionality reduction(GMDR0.9) was used to assess the gene-gene and gene-environment interactions. The interaction trees were mapped using MDR(3.0.2)software.[Results] The average occupational stress score of the case group was higher than that of the control group(P < 0.05). The results of genotype distribution analysis showed that the ADD1 gene Gly460 Trp and rs17833172 sites were statistically different between the two groups(P < 0.05), and the β 2-AR gene 1023 and rs1042717 sites were not(P > 0.05). The results of logistic regression analysis showed that, after adjusting for selected confounding factors, the GG genotype at rs17833172 of ADD1 gene was a risk factor for hypertension(OR=2.948, 95%CI: 1.209-7.187, P < 0.05), and the TT genotype at Gly460 Trp of ADD1 was a protective factor for hypertension(OR=0.35,95%CI: 0.155-0.788);the associations between the other two sites and hypertension were not statistically significant(P > 0.05). The results of interaction analysis showed that the gene-gene interaction model between ADD1 Gly460 Trp/rs17833172 and β2-AR rs10427 was the optimal model(P < 0.05);the gene-environment interaction models between occupational stress and Gly460 Trp, rs17833172, 1023, and rs1042717 sites were the optimal models(P < 0.05). The tree maps showed a strong positive interaction between ADD1 Gly460 Trp site and β2-AR rs10427 site, and there were interactions between occupational stress and the four single nucleotide polymorphisms.[Conclusion] ADD1 gene rs17833172 site GG genotype may be a risk factor for hypertension, and ADD1 gene Gly460 Trp site TT genotype may be a protective factor for hypertension. The positive interaction between ADD1 gene Gly460 Trp site and β 2-AR gene rs1042717 site might increase oilfield workers’ hypertension risk. The interactions between occupational stress and ADD1 gene Gly460 Trp and rs17833172 sites and β2-AR gene rs1042717 and 1023 sites are related to the prevalence of hypertension in oilfield workers.