首页|NLRP3基因多态性及位点间交互作用与新疆地区煤工尘肺易感性分析

NLRP3基因多态性及位点间交互作用与新疆地区煤工尘肺易感性分析

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目的 探讨核酸结合寡聚结构域样受体热蛋白结构域相关蛋白3(NLRP3)基因多态性及位点间交互作用与新疆地区煤工尘肺易感性的关联.方法 采用方便抽样方法,选择109名煤工尘肺患者作为病例组,以64名年龄、粉尘作业工龄和工种相近的未患煤工尘肺的煤矿工人作为对照组.采集2组人群血样,采用改良多重连接酶检测反应对NLRP3的单核苷酸多态性位点rs1539019、rs4612666、rs4925650和rs7525979进行基因分型.根据赤池信息量准则选择最优遗传模型.结果 在校正年龄、工龄、饮酒和吸烟等混杂因素后,非条件logistic回归分析结果显示,携带rs1539019或rs4612666的C等位基因人群罹患煤工尘肺的风险均高于携带A或T等位基因者(P值均<0.05);携带rs1539019 AA基因型或rs4612666 TT基因型人群罹患煤工尘肺风险低于携带CC基因型者(P值均<0.05);rs1539019、rs4612666最优遗传模型分别是隐性模型和加性模型,并且这种差异在Bonferroni水平下均与煤工尘肺易感性相关(P值均<0.05).未发现rs4925650和rs7525979与煤工尘肺易感性相关(P值均>0.05).吸烟人群中,rs1539019共显性模型、隐性模型、加性模型均与罹患煤工尘肺的风险下降有关联(P值均<0.05),rs4612666共显性模型、显性模型、加性模型均与罹患煤工尘肺的风险升高有关联(P值均<0.05),最优遗传模型分别为隐性模型和加性模型.不吸烟人群中,未发现rs1539019、rs4612666与煤工尘肺风险增加相关(P值均<0.05).饮酒人群中,rs4612666显性模型、加性模型均与罹患煤工尘肺的风险升高有关联(P值均<0.05),rs4925650隐性模型、超显性模型分别与罹患煤工尘肺的风险下降和升高有关联(P值均<0.05),最优遗传模型分别为显性模型和超显性模型.不饮酒人群中,rs1539019共显性模型、显性模型、隐性模型、加性模型均与煤工尘肺的罹患风险下降有关联(P值均<0.05),rs4612666共显性模型、隐性模型、加性模型均与煤工尘肺的罹患风险升高有关联(P值均<0.05),最优遗传模型分别为加性模型和隐性模型.单倍型分析结果显示,单倍型ACAC和单倍型ACGC均可降低煤工尘肺发病的风险(P值均<0.05).结论 NLRP3基因rs1539019和rs4612666位点与罹患煤工尘肺的风险有关联,可为进一步研究煤工尘肺的发病风险提供线索.
Analysis of the NLRP3 gene polymorphism and loci interaction in susceptibility to coal workers'pneumoconiosis in the Xinjiang Region
Objective To investigate the correlation of polymorphism and loci interaction of nucleic acid binding oligomeric domain-like receptor heat protein domain associated protein 3(NLRP3)gene and susceptibility to coal workers'pneumoconiosis(CWP)in Xinjiang Region.Methods A total of 109 CWP were selected as the case group,and 69 coal miners with similar age,years of dust exposure and work types were selected as the control group by convenient sampling method.Blood samples of individuals in workers in these two groups were collected,and the genotypes of single nucleotide polymorphism loci,rs1539019,rs4612666,rs4925650 and rs7525979,in the NLRP3 gene were detected using an improved multiplex ligation detection reaction.The optimal genetic model was selected based on the Akaike information criterion.Results The results of unconditional logistic regression analysis showed that individuals with the C allele of rs1539019 or rs4612666 had a higher risk of CWP than those with the A or T allele(all P<0.05),and individuals with the AA genotype of rs1539019 or the TT genotype of rs4612666 had a lower risk of CWP than those with the CC genotype(all P<0.05),after adjusting for age,years of work,alcohol,and smoking.The optimal genetic models for rs1539019 and rs4612666 were the recessive model and the additive model,respectively,and these differences were associated with the susceptibility to CWP at the Bonferroni-corrected level(all P<0.05).No correlation was found between rs4925650 and rs7525979 and the susceptibility to CWP(all P>0.05).In the smoking population,the rs1539019 co-dominant model,recessive model,and additive model were associated with a decreased risk of CWP(all P<0.05).The rs4612666 co-dominant model,dominant model and additive model were associated with an increased risk of CWP(all P<0.05),with the optimal genetic models being the recessive model and the additive model among smokers.The rs1539019 and rs4612666 were not found to be associated with the increased risk of CWP in non-smokers(all P>0.05).The rs4612666 dominant model and additive model were associated with an increased risk of CWP(all P<0.05),and the rs4925650 recessive model and over-dominant model were associated with a decreased and increased risk of developing CWP(all P<0.05),with the optimal genetic models being the dominant model and the over-dominant model in drinkers.The rs1539019 co-dominant model,dominant model,recessive model,and additive model were associated with a decreased risk of developing CWP(all P<0.05),and the rs4612666 co-dominant model,recessive model,and additive model were associated with an increased risk of developing CWP(all P<0.05),with the optimal genetic models being the additive model and the recessive model in non-drinkers.The result of haplotype analysis showed that the ACAC and ACGC haplotypes were associated with a reduced risk of CWP(all P<0.05).Conclusion The rs1539019 and rs4612666 loci of the NLRP3 gene are associated with susceptibility to CWP.This study provides clues for further research on the risk of CWP in coal workers.

Coal workers'pneumoconiosisDustGene polymorphismNLRP3InteractionGenetic model

薛茂强、许雪宇、杨成新、寇久隆、杨丹、何平

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石河子大学医学院,新疆石河子 832000

新疆维吾尔自治区第三人民医院,新疆乌鲁木齐 830091

煤工尘肺 粉尘 基因多态性 NLRP3 交互作用 遗传模型

新疆维吾尔自治区自然科学基金面上项目"天山英才"医药卫生高层次人才培养计划

2021D01A166

2024

中国职业医学
中华预防医学会 华南区域劳动卫生职业病防治中心

中国职业医学

CSTPCD
影响因子:1.011
ISSN:2095-2619
年,卷(期):2024.51(1)
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