Toll样受体4通路多态性与环境污染相互作用影响哮喘的诊断和严重程度
2018/09/10
摘要
哮喘是一种常见的慢性肺部疾病，其发病率和严重程度可能受基因-环境相互作用的影响。我们的目的是研究单核苷酸多态性（SNP）、Toll样受体4（TLR4）通路中SNP的组合、以道路到居住房屋距离作为交通相关空气污染暴露的代表指标、以及哮喘诊断和恶化之间的相关性。我们从环境多态性登记处获得了基因型、居住地址、哮喘诊断和恶化的个体水平的数据。受试者(n=2704)根据TLR4途径中的SNP基因组合被分成三组(高应答者、低应答者和无应答者)。我们对受试者进行了地理编码，计算了距离居住地与最近的主要道路之间的距离，分别为＜250m或≥250m。用logistic回归分析基因型、距道路的距离和哮喘诊断及恶化几率之间的关系。距主要道路<250m的高反应者的哮喘诊断机率为2.37（0.97，6.01），与参考组相比（p<0.10）。与无应答者相比，距离最近道路≥250米的低应答哮喘患者的活动受限率（0.46[0.21，0.95]）和失眠率（0.36[0.12，0.91]）较低（p<0.05）。特定的基因型与个体距离道路的远近（可能是与交通相关的空气污染暴露相关），可能影响哮喘诊断和恶化的可能性。
Toll-like Receptor 4 Pathway Polymorphisms Interact with Pollution to Influence Asthma Diagnosis and Severity.
Schurman SH, Bravo MA, Innes CL, Jackson WB, McGrath JA, Miranda ML, Garantziotis S.
Abstract
Asthma is a common chronic lung disease, the incidence and severity of which may be influenced by gene-environment interactions. Our objective was to examine associations between single nucleotide polymorphisms (SNPs) and combinations of SNPs in the toll-like receptor 4 (TLR4) pathway, residential distance to roadway as a proxy for traffic-related air pollution exposure, and asthma diagnosis and exacerbations. We obtained individual-level data on genotype, residential address, and asthma diagnosis and exacerbations from the Environmental Polymorphisms Registry. Subjects (n = 2,704) were divided into three groups (hyper-responders, hypo-responders, and neither) based on SNP combinations in genes along the TLR4 pathway. We geocoded subjects and calculated distance, classified as <250 m or ≥250 m, between residence and nearest major road. Relationships between genotype, distance to road, and odds of asthma diagnosis and exacerbations were examined using logistic regression. Odds of an asthma diagnosis among hyper-responders <250 m from a major road was 2.37(0.97, 6.01) compared to the reference group (p < 0.10). Hypo-responders ≥250 m from the nearest road had lower odds of activity limitations (0.46 [0.21, 0.95]) and sleeplessness (0.36 [0.12, 0.91]) compared to neither-responders (p < 0.05). Specific genotype combinations when combined with an individual's proximity to roadways, possibly due to traffic-related air pollution exposure, may affect the likelihood of asthma diagnosis and exacerbations.
哮喘是一种常见的慢性肺部疾病，其发病率和严重程度可能受基因-环境相互作用的影响。我们的目的是研究单核苷酸多态性（SNP）、Toll样受体4（TLR4）通路中SNP的组合、以道路到居住房屋距离作为交通相关空气污染暴露的代表指标、以及哮喘诊断和恶化之间的相关性。我们从环境多态性登记处获得了基因型、居住地址、哮喘诊断和恶化的个体水平的数据。受试者(n=2704)根据TLR4途径中的SNP基因组合被分成三组(高应答者、低应答者和无应答者)。我们对受试者进行了地理编码，计算了距离居住地与最近的主要道路之间的距离，分别为＜250m或≥250m。用logistic回归分析基因型、距道路的距离和哮喘诊断及恶化几率之间的关系。距主要道路<250m的高反应者的哮喘诊断机率为2.37（0.97，6.01），与参考组相比（p<0.10）。与无应答者相比，距离最近道路≥250米的低应答哮喘患者的活动受限率（0.46[0.21，0.95]）和失眠率（0.36[0.12，0.91]）较低（p<0.05）。特定的基因型与个体距离道路的远近（可能是与交通相关的空气污染暴露相关），可能影响哮喘诊断和恶化的可能性。
(中日友好医院呼吸与危重症医学科 李红雯 摘译 林江涛 审校)
(Sci Rep. 2018 Aug 23;8(1):12713.)
(Sci Rep. 2018 Aug 23;8(1):12713.)
Toll-like Receptor 4 Pathway Polymorphisms Interact with Pollution to Influence Asthma Diagnosis and Severity.
Schurman SH, Bravo MA, Innes CL, Jackson WB, McGrath JA, Miranda ML, Garantziotis S.
Abstract
Asthma is a common chronic lung disease, the incidence and severity of which may be influenced by gene-environment interactions. Our objective was to examine associations between single nucleotide polymorphisms (SNPs) and combinations of SNPs in the toll-like receptor 4 (TLR4) pathway, residential distance to roadway as a proxy for traffic-related air pollution exposure, and asthma diagnosis and exacerbations. We obtained individual-level data on genotype, residential address, and asthma diagnosis and exacerbations from the Environmental Polymorphisms Registry. Subjects (n = 2,704) were divided into three groups (hyper-responders, hypo-responders, and neither) based on SNP combinations in genes along the TLR4 pathway. We geocoded subjects and calculated distance, classified as <250 m or ≥250 m, between residence and nearest major road. Relationships between genotype, distance to road, and odds of asthma diagnosis and exacerbations were examined using logistic regression. Odds of an asthma diagnosis among hyper-responders <250 m from a major road was 2.37(0.97, 6.01) compared to the reference group (p < 0.10). Hypo-responders ≥250 m from the nearest road had lower odds of activity limitations (0.46 [0.21, 0.95]) and sleeplessness (0.36 [0.12, 0.91]) compared to neither-responders (p < 0.05). Specific genotype combinations when combined with an individual's proximity to roadways, possibly due to traffic-related air pollution exposure, may affect the likelihood of asthma diagnosis and exacerbations.
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Th2型生物标志物在重症哮喘中的分离；主要由FeNO作为恶化的预测因子，骨膜蛋白作为肺功能降低的预测因子
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第一次病毒感染引发喘息发作4年后肺功能及气道反应性变化
