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新疆醫(yī)務工作者職業(yè)緊張與高血壓發(fā)病狀況及其表觀遺傳學研究

發(fā)布時間:2018-08-08 20:55
【摘要】:目的:調(diào)查新疆三甲醫(yī)院醫(yī)務人員職業(yè)緊張水平,生理、心理健康狀況等基本情況,采取病例對照研究探討醫(yī)務人員EMILIN1、SLC6A2基因多態(tài)性和高血壓易感性的相關(guān)性及職業(yè)緊張交互作用在高血壓人群中的致病作用,比較不同緊張程度和血壓水平狀態(tài)下NET基因啟動子區(qū)DNA甲基化的差異,探討表觀遺傳學在職業(yè)緊張與高血壓相關(guān)性中的調(diào)控作用。完善新疆地區(qū)醫(yī)務人員職業(yè)緊張和健康狀況的流行病學資料,為制定和提高醫(yī)務人員的身心健康水平、防治高血壓提供科學依據(jù)。方法:1)本研究采取整群抽樣抽取新疆三級甲等醫(yī)院的醫(yī)務人員2036人作為研究對象,進行工作緊張測量量表(Job stress survey,JSS)、工作倦怠、工作投入調(diào)查問卷和慢性非傳染性疾病現(xiàn)患情況及行為危險因素調(diào)查問卷的現(xiàn)況調(diào)查;2)采用病例對照研究,應用聚合酶鏈式反應限制性片段長度多態(tài)法(polymerasechain reaction-restriction fragment length polymorphism,PCR-RFLP),檢測確診為高血壓的200名病例組和200名對照組(匹配同性別、年齡±3歲、同民族)的基因多態(tài)性;3)采用亞硫酸氫鹽克隆測序法處理基因組DNA,隨后設計BSP引物進行PCR,并對PCR產(chǎn)物進行測序判斷Cp G位點是否發(fā)生甲基化。結(jié)果:1)共發(fā)放調(diào)查問卷2036份,收回有效合格問卷1847份,回收率為90.7%。男性職業(yè)緊張各維度得分均高于女性(P0.05);不同工齡職業(yè)緊張各維度得分均不同(P0.05);工齡10-20年組職業(yè)緊張各維度得分最高(P0.05);男性在工作倦怠及各維度得分均高于女性,女性在工作投入及精力和奉獻2個維度得分均高于男性(P0.05);工齡10-20年組工作倦怠中情緒耗竭、去個性化得分最高,工齡20年組工作投入中奉獻得分最高(P0.05);不同科室職業(yè)緊張各維度得分均不同(P0.05);外科、婦產(chǎn)科組除了工作壓力強度與內(nèi)科、兒科組差異無統(tǒng)計學意義,其余職業(yè)緊張各維度得分均高于內(nèi)科、兒科組(P0.05);外科、婦產(chǎn)組和內(nèi)科、兒科組職業(yè)緊張各維度得分均高于醫(yī)技組(P0.05);不同職稱職業(yè)人群職業(yè)緊張各維度得分均不同,中級職稱職業(yè)緊張各維度得分最高(P0.05);外科、婦產(chǎn)科組在工作倦怠總分、情緒耗竭2項得分均高于內(nèi)科、兒科組和醫(yī)技組(P0.05);不同職業(yè)緊張水平醫(yī)務人員在工作倦怠總分、情緒耗竭、去個性化、個人成就感降低得分均不同(P0.05);情緒耗竭、個人成就感降低得分中,高度和中度緊張組均高于低度組緊張組(P0.05);去個性化得分中,高度緊張組得分最高(P0.05);不同職業(yè)緊張水平,醫(yī)務人員在奉獻得分不同(P0.05);經(jīng)LSD兩兩比較,其中奉獻的得分中,高度和中度緊張組的得分低于低度緊張組(P0.05);職業(yè)緊張各項得分與工作倦怠總分、情緒耗竭得分呈正相關(guān),與奉獻得分呈負相關(guān)(P0.01);工作緊張指數(shù)、工作壓力指數(shù)、組織支持缺乏指數(shù)與去個性化得分呈正相關(guān)(P0.05);2)本次調(diào)查的醫(yī)務人員中,慢病患病居前7位的依次是:頸、腰部疾病(24.6%)、慢性消化系統(tǒng)疾病(21.5%)、高血壓(14.9%)、高血脂(10.1%)、呼吸系統(tǒng)疾病(8.0%)、慢性泌尿系統(tǒng)疾病(5.2%)、甲狀腺疾病(4.1%);不同工齡組的頸、腰部疾病、慢性消化系統(tǒng)疾病、高血壓、高血脂患病率隨著工齡的增加而增加(P0.05);不同職業(yè)緊張水平組的頸、腰部疾病、慢性消化系統(tǒng)疾病、高血壓、高血脂患病率不同(P0.05);采用兩分類Logistic回歸分析方法得出患有慢性消化系統(tǒng)疾病和高血脂是高血壓患病的危險因素。工作緊張指數(shù)、工作壓力指數(shù)、情緒耗竭及去個性化每增加1個單位,醫(yī)務人員患高血壓的可能性分別增加6.172、5.134、6.805、4.470倍;3)病例組的總膽固醇、空腹血糖均高于對照組(P0.05);病例組與對照組在高血壓遺傳史、被動吸煙、食鹽、夜班頻率、睡眠質(zhì)量、職業(yè)緊張水平,差異有統(tǒng)計學意義(P0.05);病例組在職業(yè)緊張各維度得分均高于對照組(P0.05);4)rs2304682位點各個基因型和等位基因在病例組和對照組分布差異有統(tǒng)計學意義(P0.05);rs2397771位點等位基因在病例組和對照組分布差異有統(tǒng)計學意義(P0.05);在調(diào)整了遺傳史、被動吸煙、食鹽、睡眠質(zhì)量、夜班頻率、職業(yè)緊張水平影響后,以rs2304682位點CC基因型為參照,攜帶GG基因型發(fā)生高血壓的風險增加(OR=2.611,95%CI:1.190-5.727);以rs2304682位點CC+CG基因型為參照,攜帶GG基因型發(fā)生高血壓的風險增加(OR=2.432,95%CI:1.156-5.118);以rs2397771位點GG基因型為參照,攜帶GC基因型發(fā)生高血壓的風險增加(OR=1.731,95%CI:1.057-2.835);以rs2397771位點GG基因型為參照,攜帶GC+CC基因型發(fā)生高血壓的風險增加(OR=1.703,95%CI:1.081-2.683);5)采用非條件多因素Logistic回歸分析基因-基因、基因-環(huán)境交互作用發(fā)現(xiàn):rs2304682與rs2397771、rs2304682與職業(yè)緊張、rs2397771與職業(yè)緊張基于相乘模型交互作用不具有統(tǒng)計學意義(P0.05);采用GMDR分析基因-基因、基因-環(huán)境交互作用發(fā)現(xiàn):rs2304682-rs2397771模型均具有統(tǒng)計學意義(P0.05);職業(yè)緊張-夜班頻率,rs2397771-職業(yè)緊張-夜班頻率兩個模型均具有統(tǒng)計學意義(P0.001);其中rs2397771-職業(yè)緊張-夜班頻率模型為基因-環(huán)境交互作用最佳模型;6)醫(yī)務人員職業(yè)緊張-高血壓-基因的關(guān)聯(lián)研究提示本次調(diào)查的高血壓產(chǎn)生與各因素間的復雜關(guān)聯(lián)中,職業(yè)緊張、基因多態(tài)性與高血壓產(chǎn)生間存在較強的顯著關(guān)聯(lián),同時生活習慣等因素是間接影響因素;7)NET基因啟動子區(qū)Cp G1及Cp G7各組之間經(jīng)方差分析,差異有統(tǒng)計學意義(P0.05)。經(jīng)LSD兩兩比較,對照組-高職業(yè)緊張組、高血壓-高職業(yè)緊張組甲基化水平高于高血壓-低職業(yè)緊張組,差異有統(tǒng)計學意義(P0.05)。其他Cp G位點均無統(tǒng)計學意義。結(jié)論:1)醫(yī)務人員中男性、工齡在10-20年組,且外科、婦產(chǎn)科組職業(yè)緊張、倦怠水平最高,中級職稱職業(yè)緊張水平最高;女性在工作投入及精力和奉獻2個維度得分均高于男性,醫(yī)務人員職業(yè)緊張狀況與性別、工齡、科室及職稱等個體特征相關(guān)。職業(yè)緊張越高的醫(yī)務人員,職業(yè)倦怠越高;職業(yè)緊張水平越高工作投入水平越低。工齡和職業(yè)緊張可能是影響醫(yī)務人員患慢性疾病的危險因素。慢性消化系統(tǒng)疾病、高血脂、工作緊張指數(shù)、工作壓力指數(shù)、情緒耗竭及去個性化是高血壓患病的危險因素。建議醫(yī)院應積極干預和降低醫(yī)務人員職業(yè)緊張程度,降低心理健康風險,增加應對資源,加強自我保健和修養(yǎng),定期開展心理健康教育活動;2)本研究的對照組人群單核苷酸多態(tài)性(single nucleotide polymorphism,SNP)各多態(tài)性位點的基因型分布均符合新疆地區(qū)少數(shù)民族人群中的等位基因頻率接近,進一步提示由于研究對象選擇導致基因型在人群分布產(chǎn)生偏倚的可能性較小,結(jié)果可靠;EMILIN1基因rs2304682及SLC6A2基因rs2397771兩個SNP位點和職業(yè)緊張、遺傳史、被動吸煙、食鹽、睡眠質(zhì)量、夜班頻率6個因素存在基因-環(huán)境交互作用。因此在預防高血壓的過程中,對于存在遺傳易感性的個體時,應避免外界高危因素的刺激。降低醫(yī)務人員職業(yè)緊張水平,減少夜班頻率可以預防易感人群高血壓的發(fā)生;生活習慣可能通過職業(yè)緊張因素的影響而共同對基因多態(tài)性產(chǎn)生影響,進而對高血壓的產(chǎn)生進行影響。這能夠為今后醫(yī)務人員心理健康及高血壓產(chǎn)生等問題的干預提供有效干預措施建議;3)職業(yè)緊張組中高血壓醫(yī)務人員其NET基因啟動子區(qū)Cp G1及Cp G7位點DNA甲基化水平與對照組存在差異,提示表觀遺傳學在職業(yè)緊張與高血壓相關(guān)性中具有調(diào)控作用。
[Abstract]:Objective: To investigate the basic situation of occupational stress level, physiology and mental health status of medical staff in Xinjiang three a hospital, and to investigate the correlation between EMILIN1, SLC6A2 gene polymorphism and susceptibility to hypertension, and the pathogenicity of occupational stress interaction in high blood pressure population. The difference of DNA methylation in the promoter region of NET gene in the state of blood pressure level is used to explore the regulatory role of epigenetics in the relationship between occupational stress and hypertension. To improve the epidemiological data of occupational stress and health status of medical workers in Xinjiang, to provide science for the formulation and improvement of medical staff's physical and mental health and the prevention and treatment of hypertension. Methods: 1) in this study, 2036 medical staff of Grade A hospitals in Xinjiang three were selected as the research subjects, and the work stress scale (Job stress survey, JSS), job burnout, work input questionnaire and the current situation survey of chronic non communicable diseases and behavioral risk factors were investigated; 2) Using a case-control study, polymerasechain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the genetic polymorphism of 200 cases of hypertension and 200 control groups (matching the same sex, age 3 years, the same nation); 3) the use of hydrogen sulfite salt. Cloning sequencing method treated genomic DNA, then designed BSP primers for PCR, and sequenced PCR products to determine whether Cp G loci was methylation. Results: 1) a total of 2036 questionnaires were issued and 1847 valid questionnaires were recovered. The recovery rate was higher than that of women (P0.05) in 90.7%. male occupational stress and occupational stress at different working age. The scores of all dimensions were all different (P0.05); the scores of all dimensions of occupational stress in the 10-20 year group were the highest (P0.05); the scores of men in job burnout and all dimensions were higher than those of women. The scores of women in work input and energy and dedication were higher than men (P0.05); the job burnout in 10-20 years of working age group was the highest, and the highest score of individualization was in the work age. The score of dedication in the 20 year group was the highest (P0.05); the scores of various dimensions of occupational stress in different departments were all different (P0.05); there was no statistical difference between the Department of surgery and the Department of Obstetrics and Gynecology, except for the work stress intensity and internal medicine, and the other occupational stress dimensions were higher than that of the internal department, the pediatric group (P0.05), the surgery, obstetrics and Gynecology, and the pediatrics group. The scores of all dimensions were higher than that of the medical technology group (P0.05); the scores of occupational stress in different occupational groups were all different, the scores of the occupational stress of the intermediate titles were the highest (P0.05); the 2 scores of job burnout and emotional exhaustion in the surgery, obstetrics and Gynecology group were all higher than those of the internal department, the pediatrics group and the medical skill group (P0.05); The total scores of job burnout, emotional exhaustion, individualization, and personal achievement reduction were all different (P0.05); in the scores of emotional exhaustion and personal accomplishment reduction, both high and moderate tension groups were higher than those in the low group tension group (P0.05); the high tension group scored highest (P0.05) in the individualized score (P0.05); the different occupational stress levels and medical staff were in the score. The score of dedication was different (P0.05); among the scores of LSD 22, the scores of the high and moderate tension groups were lower than the low tension group (P0.05); the scores of occupational stress were positively correlated with the total score of job burnout, the scores of emotional exhaustion, and the score of dedication (P0.01); the work stress index, the work stress index, and the organizational support were lacking. There was a positive correlation between the lack of index and depersonalization (P0.05); 2) among the medical workers in this survey, the top 7 of the chronic diseases were: neck, waist disease (24.6%), chronic digestive system disease (21.5%), hypertension (14.9%), hyperlipidemia (10.1%), respiratory system disease (8%), chronic urinary system disease (5.2%), thyroid disease (4.1%); different working age. The prevalence of cervix, lumbar disease, chronic digestive system disease, hypertension and hyperlipidemia increased with age (P0.05); the prevalence rates of neck, waist, chronic digestive system, hypertension and hyperlipidemia in different occupational stress groups were different (P0.05); the chronic digestive system was obtained by two classification Logistic regression analysis. Disease and hyperlipidemia were the risk factors of hypertension. Working stress index, working stress index, emotional exhaustion and depersonalization were increased by 1 units, the possibility of hypertension by medical staff increased 6.172,5.134,6.805,4.470 times respectively; 3) the total cholesterol and empty abdominal blood glucose in the case group were higher than those of the control group (P0.05); case group and control group were higher than those in control group. In the genetic history of hypertension, passive smoking, salt, night shift frequency, sleep quality, occupational stress level, the difference was statistically significant (P0.05); the scores of occupational stress in the case group were higher than those in the control group (P0.05); 4) the differences in the genotype and allele of the rs2304682 locus were statistically significant (P0.05) in the case group and the control group (P0.05); rs2397 The distribution difference between the 771 loci alleles in the case group and the control group was statistically significant (P0.05). After adjusting the genetic history, passive smoking, salt, sleep quality, night shift frequency, and occupational stress level, the risk of carrying GG genotype hypertension increased (OR=2.611,95%CI:1.190-5.727) with the GG genotype CC genotype (OR=2.611,95%CI:1.190-5.727); RS The 2304682 locus CC+CG genotype was used as a reference, and the risk of carrying GG genotype increased (OR=2.432,95%CI:1.156-5.118); the risk of carrying high blood pressure with the GC genotype increased (OR=1.731,95%CI:1.057-2.835) with the rs2397771 genotype GG genotype as a reference, with the GG genotype of rs2397771 site as a reference to carry the GC+CC genotypes to occur high blood. The risk of pressure increased (OR=1.703,95%CI:1.081-2.683); 5) the use of non conditional multiple factor Logistic regression analysis gene gene, gene environmental interaction found that rs2304682 and rs2397771, rs2304682 and occupational stress, rs2397771 and occupational stress based on the multiplicative model interaction did not have statistical significance (P0.05); GMDR analysis gene - base Because of gene environmental interaction, the rs2304682-rs2397771 model was statistically significant (P0.05); occupational stress - night shift frequency, rs2397771- occupational stress - night shift frequency two models were statistically significant (P0.001), and rs2397771- occupational stress - night shift rate model was the best model of gene environmental interaction; 6) medical workers The association of occupational stress - hypertension - genes suggests that there is a strong correlation between occupational stress, genetic polymorphism and hypertension, and the factors of living habits are indirect factors, and 7) the NET gene promoter region Cp G1 and Cp G7 between each group. Difference analysis, the difference was statistically significant (P0.05). Compared with LSD 22, the control group, high occupational stress group, high hypertension and high occupational stress group was higher than hypertension and low occupational stress group, the difference was statistically significant (P0.05). The other Cp G loci were not statistically significant. Conclusion: 1) the male in the medical staff was in the 10-20 year group, and the surgery was in the surgery. In the obstetrics and Gynecology group, the level of occupational stress and burnout was the highest and the level of occupational stress was the highest. The scores of 2 dimensions of work input, energy and dedication were all higher than that of men. The occupational stress of medical staff was related to the individual characteristics of sex, work age, department and title. The higher the occupational stress, the higher the job burnout, and the occupational stress. The higher the level of Zhang Shuiping's work, the lower the level of work. Working age and occupational stress may be the risk factors that affect the medical staff with chronic diseases. Chronic digestive system diseases, hyperlipidemia, work stress index, work stress index, emotional exhaustion and depersonalization are risk factors for hypertension. It is suggested that hospitals should actively intervene and reduce medical workers. The degree of occupational stress, reducing the risk of mental health, increasing the coping resources, strengthening self health care and cultivation, carrying out mental health education regularly; 2) the genotype distribution of the polymorphisms of single nucleotide polymorphisms (single nucleotide polymorphism, SNP) in the control group of this study conforms to the minority ethnic groups in Xinjiang region. The allele frequency is close, and further hints that the possibility of genetic bias in the population distribution is smaller and the result is reliable. The two SNP loci of the EMILIN1 gene rs2304682 and SLC6A2 gene rs2397771, the genetic history, the passive smoking, the salt eating, the sleep quality, and the night shift frequency exist in the gene environment. Therefore, in the process of prevention of hypertension, for individuals with genetic susceptibility, it is necessary to avoid the stimulation of high risk factors of the outside world. Reducing the occupational stress level and reducing the frequency of night shift can prevent the occurrence of hypertension in the susceptible population; life habits may pass through the influence of occupational stress factors and share more genes. The influence of the state of state on the production of hypertension, which can provide effective intervention suggestions for the intervention of medical workers' mental health and hypertension and other problems in the future. 3) the level of Cp G1 and Cp G7 site DNA methylation in the NET gene promoter region of the occupational stress group is different from that of the control group. Epigenetics plays a regulatory role in the relationship between occupational stress and hypertension.
【學位授予單位】:新疆醫(yī)科大學
【學位級別】:博士
【學位授予年份】:2015
【分類號】:R544.1

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