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CAT基因多态性与噪声性听力损失发生风险的分子流行病学研究

发布时间:2018-01-21 01:15

  本文关键词: 噪声性听力损失 CAT基因 遗传变异 分子流行病学研究 出处:《南京医科大学》2012年硕士论文 论文类型:学位论文


【摘要】:噪声性听力损失(noise-induced hearing loss, NIHL)是最重要的职业危害之一,已成为世界范围内普遍的职业健康高危因素和第二常见的感觉神经性听力损失,仅次于年龄相关性听力损失(age-related hearing loss,ARHL)。中国卫生部职业病年度报告显示,每年新增的职业病病人中,有1/6来自于NIHL,60%以上的工厂企业都存在噪声危害,,给工厂企业和噪声作业人员带来了沉重的经济负担和严重的健康损害。个体易感性差异是NIHL最显著的特点,它受遗传和环境因素共同影响。许多学者认为氧化应激是NIHL的潜在机制,其产生大量的活性氧自由基可导致毛细胞损伤和死亡。过氧化氢酶(catalase, CAT)是在生物演化过程中建立起来的生物防御系统的关键酶之一,它最重要的生理功能为参与活性氧自由基代谢过程,维持体内氧化-抗氧化平衡。CAT基因多态性可能与该酶的活性及转录活性有关,从而影响个体间对NIHL的易感性不同。因此,我们推测CAT基因可能是NIHL的易感基因之一。 本研究选择2010年9月至2011年5月分别在中国石化仪征化纤股份有限公司、徐州大屯煤电公司及南京晨光集团有限责任公司参加职业卫生体检的工人作为研究对象,其中病例615例,对照1514例(匹配对照644例)。取5ml外周血,并分离血清,利用天根试剂盒提取DNA。基于NCBI数据库选取CAT基因功能区的4个SNP(ssingle nucleotide polymorphisms, SNPs)位点,即rs564250、rs769214、rs7943316和rs769217。采用TaqMan探针方法对SNPs进行基因分型,可见光法测定血清中CAT活性。多因素非条件Logistic回归模型计算各基因型人群发生NIHL的比值比(odds ratios, ORs)及其95%可信区间(confidenceintervals, CIs),最终评价CAT基因多态变异在NIHL发生风险中的作用。 结果显示,CAT活性在NIHL病例与对照人群具有统计学差异(P=0.045)。各多态位点的基因型分布在病例组与对照组中无统计学差异;建立显性模型分层分析,与携带rs564250CC基因型相比,在小年龄(35岁)(OR=0.47,95%CI=0.27-0.80)、不吸烟(OR=0.64,95%CI=0.44-0.93)、女性(OR=0.27,95%CI=0.11-0.66)人群中携带rs564250CT/TT联合基因型对NIHL的发生具有保护作用;吸烟人群携带rs769214AG/AA或rs7943316AT/TT联合基因型均可降低NIHL的发生风险(rs769214: OR=0.69,95%CI=0.52-0.93; rs7943316: OR=0.73,95%CI=0.55-0.98)。吸烟人群中,对于rs769214位点,携带AG和AA基因型个体发生NIHL的风险低于携带GG基因型的个体(AG: OR=0.73,95%CI=0.54-0.99; AA: OR=0.50,95%CI=0.29-0.87)。显性模型分层分析结果显示:携带rs769214AG/AA、rs7943316AT/TT联合基因型在短时间(≤20年)暴露人群(rs769214: OR=0.65,95%CI=0.45-0.96; rs7943316: OR=0.67,95%CI=0.46-0.98)与高水平(92dB)暴露人群(OR=0.51,95%CI=0.32-0.83)发生NIHL的风险均降低。 上述结果表明:CAT基因遗传变异与中国汉族吸烟人群NIHL的易感明显关联,此研究结果尚需大样本研究和后续功能学的进一步验证。
[Abstract]:Noise-induced hearing loss (NIHLs) is one of the most important occupational hazards. It has become a worldwide high risk factor for occupational health and the second most common sensory neurotic hearing loss. Second only to age-related hearing loss. Annual report on Occupational Diseases of Ministry of Health of China. Every year, more than 60% of the new occupational disease patients come from NIHL 60% of the factory enterprises have noise hazards. It brings heavy economic burden and serious health damage to factory enterprises and noise workers. Individual susceptibility difference is the most significant characteristic of NIHL. It is influenced by both genetic and environmental factors. Many scholars believe that oxidative stress is the underlying mechanism of NIHL. It produces a large number of reactive oxygen free radicals can lead to hair cell damage and death. CAT is one of the key enzymes of biological defense system established in the process of biological evolution. Its most important physiological function is to participate in the metabolism of reactive oxygen free radicals. Maintaining oxidation-antioxidant balance. Cat gene polymorphism may be related to the enzyme activity and transcriptional activity, thus affecting the susceptibility of individuals to NIHL. We speculate that CAT gene may be one of the susceptible genes of NIHL. This study selected September 2010 to May 2011 in Sinopec Yizheng Chemical Fiber Co., Ltd. respectively. Xuzhou Datun Coal and Power Company and Nanjing Chenguang Group Co., Ltd. participated in occupational health examination of workers as the study object, including 615 cases. The peripheral blood was collected from 644 cases of matched control group and the serum was isolated. DNAs were extracted by using the sky-root kit. Four SNPs of CAT gene functional region were selected based on NCBI database. Ssingle nucleotide polymorphisms. SNPs, rs564250, rs769214. Rs7943316 and rs769217. genotyping of SNPs was carried out by TaqMan probe method. The activity of CAT in serum was measured by visible light method. The ratio of NIHL to odds ratios was calculated by multivariate conditional Logistic regression model. ) and its 95% confidence intervals, CIsa, and finally evaluate the role of polymorphic variation of CAT gene in the risk of NIHL. The results showed that the activity of catalase in NIHL patients was significantly different from that in the control group (P < 0.05), and there was no significant difference in the genotype distribution of the polymorphic loci between the case group and the control group. The dominant model was established for stratified analysis. Compared with carrying rs564250CC genotypes, in the young age of 35 years old, 0.47 95% CI 0.27-0.80). No smoking, 0. 64%, 95% CI0.44-0. 93, female ORO 0. 27. 95CII 0.11-0.66) carrying the combined genotype of rs564250CT/TT has protective effect on the occurrence of NIHL. The risk of NIHL was significantly reduced in smokers with rs769214AG/AA or rs7943316AT/TT combined genotypes (P < 0.05). Rs769214: OR=0.69. 95 CIQ 0.52-0.93; Rs7943316: OR0.7395. The rs769214 locus was found in smoking population. Individuals with AG and AA genotype had lower risk of developing NIHL than those with GG genotype (AGG: OR0.7395). AA: ORO 0.50 and 95% CIQ 0.29-0.87.The results of stratification analysis of dominant model showed that rs769214AG/AA was carried. The combined genotype of rs7943316AT/TT in short time (鈮

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