本文選題：聽力損失 + 鈣黏蛋白23��； 參考：《廣東藥學院》2012年碩士論文

【摘要】：目的 了解噪聲作業(yè)工人鈣黏蛋白3（Cadherin23, CDH23）、質(zhì)膜Ca~(2+)-ATP酶異構(gòu)體2（Plasma membrane of Ca~(2+)-ATPase isoform2, PMCA2）單核苷酸多態(tài)性(Singlenucleotide polymorphism, SNP)表達，探討CDH23、PMCA2單核苷酸多態(tài)性與噪聲性聽力損失（Noise induced hearing loss, NIHL）的關(guān)系，為NIHL個體篩選提供科學依據(jù)，更好的預防NIHL發(fā)生。 方法 采用現(xiàn)場流行病學方法，對194名噪聲作業(yè)工人進行問卷調(diào)查和聽力測定，按照聽力學評價結(jié)果將其分為聽力損失組和聽力正常組。TaKaRa公司DNA抽提試劑盒提取全血DNA，Primer Premier5.0引物設(shè)計軟件分別設(shè)計CDH23及PMCA2基因SNP引物；聚合酶鏈式反應(yīng)-限制性片段長度多態(tài)性(Polymerase chain reaction fragmentlength polymorphism, PCR-RFLP)進行CDH23-rs1227049、rs1227051、rs3802711、Exon7位點及PMCA2-rs2289274位點基因型鑒別；特異性擴增法(Allele specific amplification,ASA)進行PMCA2-rs6790640位點基因型鑒別。SAS9.0進行統(tǒng)計分析，等位基因及基因型組間比較用χ2檢驗；多因素Logistic回歸分析對年齡、性別、累積噪聲暴露量等因素進行校正，計算不同基因型噪聲作業(yè)工人發(fā)生NIHL的危險度。 結(jié)果 聽力損失組94人，聽力正常組100人。兩組人群均衡性檢驗發(fā)現(xiàn)：聽力損失組與聽力正常組文化程度、噪聲暴露強度、工齡、累積噪聲暴露量差異無統(tǒng)計學意義(P0.05)；性別、年齡分布差異有統(tǒng)計學意義(P0.05)。 CDH23-rs3802711位點T等位基因是NIHL的保護因素，與C等位基因相比，OR=0.61,95%CI=0.41~0.92；Exon7位點A等位基因是NIHL的危險因素，與G等位基因相比，OR=4.65，95%CI=2.90~7.44。PMCA2-rs12289274位點G等位基因是NIHL的危險因素，與A等位基因相比，OR=2.27，95%CI=1.47~3.53；rs6790640位點T等位基因是NIHL的危險因素，與C等位基因相比，，OR=1.69，95%CI=1.12~2.53。 多因素Logistic回歸分析校正了194名研究對象的年齡、性別、累積噪聲暴露量等因素后，發(fā)現(xiàn)攜帶CDH23-rs3802711位點的CC基因型與TT基因型的個體相比，NIHL發(fā)生風險較高（OR=0.18,95％CI=0.06~049, P0.05）;攜帶CDH23-Exon7位點GG基因型與AA基因型的個體相比， NIHL發(fā)生風險較高（OR=15.87,95％CI=3.91~64.45, P0.05）。PMCA2-rs2289274位點的AG基因型與GG基因型的個體相比，NIHL發(fā)生風險較高（OR=13.60,95％CI=6.09~30.61, P0.05）。 結(jié)論 1不能認為職業(yè)噪聲暴露人群中CDH23基因rs1227049和rs1227051兩單核苷酸多態(tài)性與NIHL有關(guān)聯(lián)。 2攜帶CDH23-rs3802711位點T等位基因是NIHL的保護因素，攜帶CDH23-Exon7位點A等位基因，PMCA2-rs12289274位點G等位基因是NIHL的危險因素；進一步的基因型與NIHL關(guān)系研究發(fā)現(xiàn)，CDH23-rs3802711CT基因型是NIHL的保護因素；CDH23-Exon7GG基因型、PMCA2-rs12289274AG基因型是NIHL的危險因素。初步認為CDH23-rs3802711、CDH23-Exon7、PMCA2-rs12289274是NIHL易感性單核苷酸多態(tài)性位點。
[Abstract]:Objective to investigate the expression of single nucleotide polymorphisms (SNPs) of cadherin 3 (CDH23) and plasma membrane of Ca2 -ATPase isoform2 (PMCA2) in noise exposed workers, and to investigate the relationship between CDH23PMCA2 single nucleotide polymorphism and noise induced hearing loss, NIHL (Noise induced hearing loss, NIHL). To provide scientific basis for the screening of NIHL individuals and to prevent the occurrence of NIHL. Methods 194 workers exposed to noise were investigated and their hearing was measured by field epidemiology. According to the results of audiological evaluation, it was divided into two groups: hearing loss group and normal hearing group. The primer 5.0 primer design software for whole blood DNA extraction kit was used to design SNP primers for CDH23 and PMCA2 genes, respectively. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to identify the genotypes of CDH23-rs1227049, rs1227051, rs3802711Exon7 and PMCA2-rs2289274, and (Allele specific amplification ASA was used to identify the genotypes of PMCA2-rs6790640. Multivariate logistic regression analysis was used to calibrate age, sex and cumulative noise exposure to calculate the risk of NIHL in workers exposed to different genotypes of noise. Results there were 94 cases in hearing loss group and 100 cases in normal hearing group. The results of population balance test showed that there was no significant difference in education level, noise exposure intensity, length of service, cumulative noise exposure between hearing loss group and normal hearing group (P0.05); gender, There was significant difference in age distribution (P0.05). The T allele at CDH23-rs3802711 was the protective factor of NIHL. Compared with the G allele, OR2.90 7.44.PMCA2-rs12289274 is a risk factor for NIHL, and OR2.2795CIA 1.473.53rs6790640 T allele is a risk factor for NIHL. Multivariate logistic regression analysis adjusted 194 subjects for age, sex, cumulative noise exposure, and other factors. It was found that the CC genotype with CDH23-rs3802711 locus had a higher risk of NIHL than the individuals with TT genotype (OR0.1895 CIX 0.06 049, P0.05), and that the individuals with CDH23-Exon7 GG genotype had a higher risk of NIHL (OR15.8795CI3.91CI3.91CI3.64.45, P0.05) .PMCA2-rs2289274 locus AG gene Compared with the individuals with GG genotype, the risk of NIHL was higher (ORX 13.60N95 CI 6.0930.61, P0.05). Conclusion (1) there is no association between CDH23 gene rs1227049 and rs1227051 single nucleotide polymorphisms in occupational noise exposed population. 2 T allele carrying CDH23-rs3802711 locus is the protective factor of NIHL. The PMCA2-rs12289274 G allele of CDH23-Exon7 locus was the risk factor of NIHL, and the further study of the relationship between genotype and NIHL showed that the genotype of CDH23-rs3802711CT was the protective factor of NIHL. The PMCA2-rs12289274AG genotype of CDH23-Exon7GG genotype was the risk factor of NIHL, and the PMCA2-rs12289274AG genotype of CDH23-Exon7GG genotype was the risk factor of NIHL. It is considered that CDH23-rs3802711 CDH23-Exon7 PMCA2-rs12289274 is a single nucleotide polymorphism in susceptibility to NIHL.
【學位授予單位】：廣東藥學院
【學位級別】：碩士
【學位授予年份】：2012
【分類號】：R131

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