凋亡相关基因多态性及环境行为因素与噪声性听力损失的关联研究

发布时间：2018-03-19 12:01

本文选题：凋亡　切入点：Caspase3　出处：《石河子大学》2016年硕士论文　论文类型：学位论文

【摘要】：目的:探讨环境行为因素、细胞凋亡通路相关基因多态性与中国汉族人群噪声性听力损失(noise-induced hearing loss,NIHL)易感性之间的关联,进而分析基因-环境、基因-基因间的交互作用。为中国汉族人群易感个体的筛检,进而减少NIHL的发生,保护接触噪声工人的健康提供理论依据。方法:研究对象来自2014年杭州市1549名噪声接触工人听力损失的横断面调查,采用1∶1配对病例对照研究,病例组为电测听双耳高频平均听阈㧐25 d B(A)的工人,对照组为性别、年龄、接噪工龄、工作岗位与病例匹配且双耳所有频段听阈均≤25 d B(A)的工人,共272对。PCR-LDR法检测21个SNP位点的基因型。利用SPSS20.0统计软件包对实验数据进行统计学处理,主要采用χ2检验、t检验、单因素、多因素条件logistic回归分析等,计算相对危险度(OR)及其95%可信区间。连锁不平衡和单体型分析采用SHEsis软件进行处理,采用叉生分析进行基因-环境、基因-基因间的交互作用分析。结果:(1)环境行为因素中,文化程度、入睡时间对于NIHL的发病风险呈保护性效应,文化程度在大专及本科者NIHL的患病风险是初中及以下的0.382倍(P=0.025);入睡时间在22:00—23:00和22:00的患病风险分别是23:00者的0.477倍和0.182倍(P㩳0.001)。佩戴耳机、打电话时间为NIHL的危险因素,每天平均佩戴耳机时间0-2h者患NIHL的危险是不佩戴耳机者的2.033倍(P=0.002);平均每天打电话"g16min者患NIHL的危险是不打电话者的2.477倍(P=0.012)。(2)研究人群中除rs3769823和rs7921977不符合Hardy-Weinberg遗传平衡定律外,其余19个SNP的基因型频率分布均符合Hardy-Weinberg遗传平衡定律(P0.05)。(3)对Caspase基因多态与NIHL易感性关联的主效应分析表明,CASP3基因rs1049216、rs6948多态性降低NIHL的发病风险(ORCT+TT vs CC=0.645,95%CI=0.428~0.973;ORAC+CC vs AA=0.655,95%CI=0.431~0.995);以AC单体型作为参照,CT单体型携带者患NIHL的风险显著降低(OR=0.691,95%CI=0.501~0.954)。(4)CASP7基因rs2227310、rs12415607多态性降低NIHL的发病风险(rs2227310:ORGG vs CC=0.372,95%CI=0.200~0.693;ORGG vs CC+CG=0.397,95%CI=0.224~0.704;rs12415607:ORAA vs CC=0.36,95%CI=0.189~0.687;ORAA vs CC+AC=0.413,95%CI=0.231~0.739),而rs1127687多态性增高NIHL的发病风险(ORAG vs GG=1.605,95%CI=1.061~2.426;ORAG+AA vs GG=1.6,95%CI=1.079~2.374;ORGG+AA vs AG=0.638,95%CI=0.423~0.961);以CCG单体型作为参照,AGG单体型携带者患NIHL的风险有所降低(OR=0.772,95%CI=0.600~0.992)。(5)叉生分析表明,rs1049216、rs6948、rs2227310、rs12415607均与文化程度、入睡时间存在交互作用,文化程度越高、入睡时间越早,突变基因型的保护作用越明显(OR值变小且差异有统计学意义)。而rs1127687与耳机佩戴、打电话时间则存在交互作用,与rs1127687 GG野生基因型且不佩戴耳机、打电话时间16(min/d)的个体相比,rs1127687(AG+AA)突变基因型且佩戴耳机、打电话时间≥16(min/d)的个体患NIHL的显著风险上升(OR=2.008,95%CI=1.174~3.434;OR=2.283,95%CI=1.265~4.122)。rs1049216分别与rs6948、rs2227310、rs12415607,rs6948分别与rs2227310、rs12415607存在显著的协同作用,当其突变基因型共同存在时,会显著降低NIHL的发病风险。结论:在环境行为因素中,文化程度、入睡时间是NIHL的保护因素,佩戴耳机、打电话时间为NIHL的危险因素。CASP3、CASP7基因多态及其单体型与NIHL存在显著关联。CASP3和CASP7与文化程度、入睡时间、佩戴耳机与否、打电话时间等环境因素对NIHL易感性的影响存在交互作用。CASP3、CASP7存在基因-基因交互效应。研究结果仍需大样本、多中心的流行病学研究予以验证。
[Abstract]:Objective: To study the environmental behavior factors, cell apoptosis related gene polymorphism of Han population and Chinese noise induced hearing loss (noise-induced hearing, loss, NIHL) and the association between the susceptibility, analysis of gene environment and gene interaction between genes. For the Han nationality population China susceptible individual screening, and reduce the incidence of NIHL and the theoretical foundation of the protection of the health of workers exposed to noise. Methods: a cross-sectional survey study from Hangzhou city in 2014 1549 noise exposed workers hearing loss, with 1: 1 matched case-control study, cases of the disease group high frequency audiometry binaural average hearing threshold of 25 D? B (A) and the control group for sex workers, age, length of exposure to noise, jobs and case, and ears all the bands were less than 25 D B threshold (A) of the workers, a total of 272 genotypes of.PCR-LDR 21 loci of SNP. Using the SPSS20.0 statistical software package The experimental data were statistically treated mainly by 2 test, t test, single factor and multi factor Logistic regression analysis, calculated the relative risk (OR) and 95% confidence intervals. Linkage disequilibrium and haplotype analysis were processed by SHEsis software, using crossover analysis of gene environment interaction analysis the gene between genes. Results: (1) the degree of cultural factors, environmental behavior, sleep time for the risk of NIHL showed a protective effect, the degree of culture in college and undergraduate NIHL risk is 0.382 times higher than the junior middle school and the following (P=0.025); sleep time at 22:00, 23:00 and 22:00 in risk are 0.477 times and 0.182 times the 23:00 (P? 0.001). Wear the headset, call time are risk factors for NIHL, the average risk of wearing the headset 0-2h hours a day with NIHL is 2.033 times not to wear ear machine (P=0.002); the average 2.477 times not to call the phone "g16min dangerous playing with NIHL every day (P=0.012). (2) in the study population except rs3769823 and rs7921977 Hardy-Weinberg does not comply with the law of genetic equilibrium, the distribution of genotype frequencies of the remaining 19 SNP are in accordance with the Hardy-Weinberg law of genetic equilibrium (P0.05). (3) the main effect of Caspase gene polymorphism and NIHL susceptibility analysis showed that CASP3 gene rs1049216, rs6948 polymorphism decreased risk of NIHL (ORCT+TT vs CC=0.645,95%CI=0.428~0.973; ORAC+CC vs; AC AA=0.655,95%CI=0.431~0.995) to monomer type as a reference, significantly reduced the risk of CT haplotypes with NIHL (OR=0.691,95%CI=0.501~0.954). (4) CASP7 gene rs2227310. Rs12415607 polymorphism decreased risk of NIHL (rs2227310:ORGG vs CC=0.372,95%CI=0.200~0.693 ORGG; vs CC+CG=0.397,95%CI=0.224~ 0.704; rs12415607:ORAA vs CC=0.36,9 5%CI=0.189~0.687; ORAA vs CC+AC=0.413,95%CI=0.231~0.739), and rs1127687 polymorphism increased risk of NIHL (ORAG vs GG=1.605,95%CI=1.061~2.426; ORAG+AA vs GG=1.6,95%CI=1.079~2.374; ORGG+AA vs; AG=0.638,95%CI=0.423~0.961) with CCG haplotype as reference, the AGG haplotype carriers with the risk of NIHL decreased (OR=0.772,95%CI=0.600~0.992). (5) the stratify analysis showed that rs1049216, rs6948. Rs2227310, rs12415607 and cultural level, the interaction between the sleep time, the higher level of education, sleep time more early, the protective effect of genotype is more obvious (OR value becomes smaller and the difference was statistically significant.) rs1127687 and headset, call time there is an interaction between rs1127687 and GG wild genotype and do not wear the headset, call 16 (min/d) individuals compared to rs1127687 (AG+AA) gene mutation type and wear the headset, Call time = 16 (min/d) significantly increased the risk of individuals suffering from NIHL (OR=2.008,95%CI=1.174~3.434; OR=2.283,95%CI=1.265~4.122).Rs1049216 respectively with rs6948, rs2227310, rs12415607, rs6948 and rs2227310 respectively, rs12415607 has obvious synergistic effect, when the mutated genes exist together, will significantly reduce the risk of NIHL. Conclusion: in the environmental behavior factors, cultural degree, sleep time is a protective factor of NIHL, wearing a headset, call for.CASP3 NIHL risk factors, CASP7 gene polymorphisms and haplotypes with NIHL.CASP3 and CASP7 was significantly associated with the level of education, sleep time, wearing a headset or not, affect the call time and other environmental factors on susceptibility to NIHL the interaction between.CASP3, CASP7 gene gene interaction effect. The research results still need large sample, multi center epidemiological studies verified.

【学位授予单位】：石河子大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R135.8

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