本文關(guān)鍵詞： 噪聲性聽(tīng)力損失 CAT基因 遺傳變異 分子流行病學(xué)研究　出處：《南京醫(yī)科大學(xué)》2012年碩士論文　論文類(lèi)型：學(xué)位論文

【摘要】：噪聲性聽(tīng)力損失（noise-induced hearing loss, NIHL）是最重要的職業(yè)危害之一，已成為世界范圍內(nèi)普遍的職業(yè)健康高危因素和第二常見(jiàn)的感覺(jué)神經(jīng)性聽(tīng)力損失，僅次于年齡相關(guān)性聽(tīng)力損失（age-related hearing loss,ARHL）。中國(guó)衛(wèi)生部職業(yè)病年度報(bào)告顯示，每年新增的職業(yè)病病人中，有1/6來(lái)自于NIHL，60%以上的工廠企業(yè)都存在噪聲危害，，給工廠企業(yè)和噪聲作業(yè)人員帶來(lái)了沉重的經(jīng)濟(jì)負(fù)擔(dān)和嚴(yán)重的健康損害。個(gè)體易感性差異是NIHL最顯著的特點(diǎn)，它受遺傳和環(huán)境因素共同影響。許多學(xué)者認(rèn)為氧化應(yīng)激是NIHL的潛在機(jī)制，其產(chǎn)生大量的活性氧自由基可導(dǎo)致毛細(xì)胞損傷和死亡。過(guò)氧化氫酶（catalase, CAT）是在生物演化過(guò)程中建立起來(lái)的生物防御系統(tǒng)的關(guān)鍵酶之一，它最重要的生理功能為參與活性氧自由基代謝過(guò)程，維持體內(nèi)氧化-抗氧化平衡。CAT基因多態(tài)性可能與該酶的活性及轉(zhuǎn)錄活性有關(guān)，從而影響個(gè)體間對(duì)NIHL的易感性不同。因此，我們推測(cè)CAT基因可能是NIHL的易感基因之一。 本研究選擇2010年9月至2011年5月分別在中國(guó)石化儀征化纖股份有限公司、徐州大屯煤電公司及南京晨光集團(tuán)有限責(zé)任公司參加職業(yè)衛(wèi)生體檢的工人作為研究對(duì)象，其中病例615例，對(duì)照1514例（匹配對(duì)照644例）。取5ml外周血，并分離血清，利用天根試劑盒提取DNA。基于NCBI數(shù)據(jù)庫(kù)選取CAT基因功能區(qū)的4個(gè)SNP（ssingle nucleotide polymorphisms, SNPs）位點(diǎn)，即rs564250、rs769214、rs7943316和rs769217。采用TaqMan探針?lè)椒▽?duì)SNPs進(jìn)行基因分型，可見(jiàn)光法測(cè)定血清中CAT活性。多因素非條件Logistic回歸模型計(jì)算各基因型人群發(fā)生NIHL的比值比（odds ratios, ORs）及其95%可信區(qū)間（confidenceintervals, CIs），最終評(píng)價(jià)CAT基因多態(tài)變異在NIHL發(fā)生風(fēng)險(xiǎn)中的作用。 結(jié)果顯示，CAT活性在NIHL病例與對(duì)照人群具有統(tǒng)計(jì)學(xué)差異（P=0.045）。各多態(tài)位點(diǎn)的基因型分布在病例組與對(duì)照組中無(wú)統(tǒng)計(jì)學(xué)差異；建立顯性模型分層分析，與攜帶rs564250CC基因型相比，在小年齡（35歲）（OR=0.47,95%CI=0.27-0.80）、不吸煙（OR=0.64,95%CI=0.44-0.93）、女性（OR=0.27,95%CI=0.11-0.66）人群中攜帶rs564250CT/TT聯(lián)合基因型對(duì)NIHL的發(fā)生具有保護(hù)作用；吸煙人群攜帶rs769214AG/AA或rs7943316AT/TT聯(lián)合基因型均可降低NIHL的發(fā)生風(fēng)險(xiǎn)（rs769214: OR=0.69,95%CI=0.52-0.93; rs7943316: OR=0.73,95%CI=0.55-0.98）。吸煙人群中，對(duì)于rs769214位點(diǎn)，攜帶AG和AA基因型個(gè)體發(fā)生NIHL的風(fēng)險(xiǎn)低于攜帶GG基因型的個(gè)體（AG: OR=0.73,95%CI=0.54-0.99; AA: OR=0.50,95%CI=0.29-0.87）。顯性模型分層分析結(jié)果顯示：攜帶rs769214AG/AA、rs7943316AT/TT聯(lián)合基因型在短時(shí)間（≤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)與高水平（92dB）暴露人群（OR=0.51,95%CI=0.32-0.83）發(fā)生NIHL的風(fēng)險(xiǎn)均降低。 上述結(jié)果表明：CAT基因遺傳變異與中國(guó)漢族吸煙人群NIHL的易感明顯關(guān)聯(lián)，此研究結(jié)果尚需大樣本研究和后續(xù)功能學(xué)的進(jìn)一步驗(yàn)證。
[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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