噪声作业工人CDH23、PMCA2单核苷酸多态性研究

发布时间：2018-07-03 13:49

本文选题：听力损失 + 钙黏蛋白23　；参考：《广东药学院》2012年硕士论文

【摘要】：目的了解噪声作业工人钙黏蛋白3（Cadherin23, CDH23）、质膜Ca~(2+)-ATP酶异构体2（Plasma membrane of Ca~(2+)-ATPase isoform2, PMCA2）单核苷酸多态性(Singlenucleotide polymorphism, SNP)表达，探讨CDH23、PMCA2单核苷酸多态性与噪声性听力损失（Noise induced hearing loss, NIHL）的关系，为NIHL个体筛选提供科学依据，更好的预防NIHL发生。方法采用现场流行病学方法，对194名噪声作业工人进行问卷调查和听力测定，按照听力学评价结果将其分为听力损失组和听力正常组。TaKaRa公司DNA抽提试剂盒提取全血DNA，Primer Premier5.0引物设计软件分别设计CDH23及PMCA2基因SNP引物；聚合酶链式反应-限制性片段长度多态性(Polymerase chain reaction fragmentlength polymorphism, PCR-RFLP)进行CDH23-rs1227049、rs1227051、rs3802711、Exon7位点及PMCA2-rs2289274位点基因型鉴别；特异性扩增法(Allele specific amplification,ASA)进行PMCA2-rs6790640位点基因型鉴别。SAS9.0进行统计分析，等位基因及基因型组间比较用χ2检验；多因素Logistic回归分析对年龄、性别、累积噪声暴露量等因素进行校正，计算不同基因型噪声作业工人发生NIHL的危险度。结果听力损失组94人，听力正常组100人。两组人群均衡性检验发现：听力损失组与听力正常组文化程度、噪声暴露强度、工龄、累积噪声暴露量差异无统计学意义(P0.05)；性别、年龄分布差异有统计学意义(P0.05)。 CDH23-rs3802711位点T等位基因是NIHL的保护因素，与C等位基因相比，OR=0.61,95%CI=0.41~0.92；Exon7位点A等位基因是NIHL的危险因素，与G等位基因相比，OR=4.65，95%CI=2.90~7.44。PMCA2-rs12289274位点G等位基因是NIHL的危险因素，与A等位基因相比，OR=2.27，95%CI=1.47~3.53；rs6790640位点T等位基因是NIHL的危险因素，与C等位基因相比，，OR=1.69，95%CI=1.12~2.53。多因素Logistic回归分析校正了194名研究对象的年龄、性别、累积噪声暴露量等因素后，发现携带CDH23-rs3802711位点的CC基因型与TT基因型的个体相比，NIHL发生风险较高（OR=0.18,95％CI=0.06~049, P0.05）;携带CDH23-Exon7位点GG基因型与AA基因型的个体相比， NIHL发生风险较高（OR=15.87,95％CI=3.91~64.45, P0.05）。PMCA2-rs2289274位点的AG基因型与GG基因型的个体相比，NIHL发生风险较高（OR=13.60,95％CI=6.09~30.61, P0.05）。结论 1不能认为职业噪声暴露人群中CDH23基因rs1227049和rs1227051两单核苷酸多态性与NIHL有关联。 2携带CDH23-rs3802711位点T等位基因是NIHL的保护因素，携带CDH23-Exon7位点A等位基因，PMCA2-rs12289274位点G等位基因是NIHL的危险因素；进一步的基因型与NIHL关系研究发现，CDH23-rs3802711CT基因型是NIHL的保护因素；CDH23-Exon7GG基因型、PMCA2-rs12289274AG基因型是NIHL的危险因素。初步认为CDH23-rs3802711、CDH23-Exon7、PMCA2-rs12289274是NIHL易感性单核苷酸多态性位点。
[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.
【学位授予单位】：广东药学院
【学位级别】：硕士
【学位授予年份】：2012
【分类号】：R131

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