粘蛋白-5B基因多态性与煤工尘肺发病风险的相关性研究  

Study on the association between Mucin-5B gene polymorphism and the risk of coal workers’pneumoconiosis

作　　者：杨力 邓豪 陈洪云 吴玛莉 李军[1] 张涛[1,2] YANG Li;DENG Hao;CHEN Hong-yun;WU Ma-li;LI Jun;ZHANG Tao(School of Public Health,the Key Laboratory of Environmental Pollution Monitoring and Disease Control,Ministry of Education,Guizhou Medical University,Guiyang,Guizhou 561113,China;不详)

机构地区：[1]贵州医科大学公共卫生与健康学院,环境污染与疾病监控教育部重点实验室,贵州贵阳561113 [2]贵阳市公共卫生救治中心职业病科 [3]贵州中医药大学基础医学院形态学实验室

出　　处：《现代预防医学》2024年第24期4459-4464,共6页Modern Preventive Medicine

基　　金：贵州省科技计划项目(黔科合支撑[2020]4Y152号)、贵州省科技计划项目(黔科合支撑[2021]一般433)。

摘　　要：目的探讨粘蛋白-5B(MUC5B)基因表达及其位点多态性rs2075853、rs4963059和rs2014486与煤工尘肺相关性。方法通过对2020年2月—2023年10月贵阳市公共卫生救治中心506名受检者(包括143名健康对象、132名接尘工人、121名煤工尘肺壹期患者和110名煤工尘肺贰期患者)的研究,分析各组间年龄、工龄,采用实时荧光定量聚合酶链反应(qRT-PCR)评估基因表达水平,绘制受试者工作特征曲线(ROC),计算ROC曲线下面积(AUC)以评估MUC5B对煤工尘肺的预测价值,通过MassARRAY Analyzer质谱仪对MUC5B rs2075853、rs4963059、rs2014486进行基因分型,分析三个单核苷酸多态性(SNPs)基因型分布频率与煤工尘肺发病风险的关联。结果研究象对年龄(H=242.198,P<0.001)、工龄(H=315.822,P<0.001)在四组间差异均有统计学意义。煤工尘肺壹期组与煤工尘肺贰期组MUC5B表达量减少,与健康组及接尘组有显著性差异(H=34.491,P<0.001),ROC曲线分析表明MUC5B可作为煤工尘肺辅助诊断指标(AUC=0.755,95%CI:0.682~0.828,P<0.001)。此外,单体型分析发现rs4963059和rs2014486位点构建的CG单体型在煤工尘肺患者中出现频率较高,显示出了明显的差异(风险比OR=1.719,95%CI:1.074~2.751,χ2=5.201,P<0.05),暗示了由rs4963059和rs2014486位点构建的CG单体型与煤工尘肺风险增加有关。结论MUC5B基因rs4963059、rs2014486构建的CG单体型与煤工尘肺发病风险密切相关。Objective To investigate the association between the expression of mucin-5B(MUC5B)gene and its locus polymorphisms rs2075853,rs4963053,and rs2014486 with coal worker’s pneumoconiosis(CWP).Methods The study analyzed age and years of service from 506 subjects(comprising 143 healthy individuals,132 dust-exposed workers,121 stage I CWP patients,and 110 stage II CWP patients)collected at the Guiyang City Public Health and Medical Center from February 2020 to October 2023.Gene expression levels were assessed using real-time quantitative polymerase chain reaction(qRT-PCR).Receiver operating characteristic(ROC)curves were plotted,and the area under the ROC curve(AUC)was calculated to evaluate the predictive value of MUC5B for CWP.Genotyping of MUC5B rs2075853,rs4963059,and rs2014486 was performed using a MassARRAY Analyzer,and the association between the three single nucleotide polymorphisms(SNPs)genotypes’distribution frequency and the risk of CWP was analyzed.Results Significant statistical differences were observed among the groups in terms of age(H=242.198,P<0.001),years of service(H=315.822,P<0.001).Expression levels of MUC5B were significantly reduced in stage I and II CWP patients compared to the healthy and dust-exposed groups(H=34.491,P<0.001).ROC curve analysis indicated that MUC5B could serve as an auxiliary diagnostic marker for CWP(AUC=0.755,95%CI:0.682-0.828,P<0.001).Furthermore,haplotype analysis revealed that the CG haplotype constructed from rs4963059 and rs2014486 was more frequent in CWP patients,showing a significant association(odds ratio OR=1.719,95%CI:1.074-2.751,χ2=5.201,P<0.05),suggesting that the CG haplotype constructed by rs4963059 and rs2014486 loci was associated with an increased risk of coal workers’pneumoconiosis.Conclusion The CG haplotype constructed by MUC5B gene rs4963059 and rs2014486 is closely related to the risk of developing coal workers’pneumoconiosis.

关 键 词：煤工尘肺 粘蛋白-5B(MUC5B) 基因多态性 单核苷酸多态性(SNP) 早期筛查 

分 类 号：R135.2[医药卫生—劳动卫生]