二异氰酸酯哮喘以及与白细胞介素4受体、CD - 14和白细胞介素13基因的基因-环境相互作用
Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14, and IL-13 genes.
作者信息
Bernstein David I, Wang Ning, Campo Paloma, Chakraborty Ranajit, Smith Andrew, Cartier André, Boulet Louis-Philippe, Malo Jean-Luc, Yucesoy Berran, Luster Michael, Tarlo Susan M, Hershey Gurjit K Khurana
机构信息
Department of Internal Medicine, Division of Immunology, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
出版信息
Ann Allergy Asthma Immunol. 2006 Dec;97(6):800-6. doi: 10.1016/S1081-1206(10)60972-6.
BACKGROUND
Diisocyanate asthma (DA) affects 2% to 10% of exposed workers, yet the pathogenetic mechanisms underlying this disorder remain ill defined.
OBJECTIVE
To determine if specific single nucleotide polymorphisms (SNPs) of interleukin 4 receptor alpha (IL4RA), IL-13, and CD14 promoter genes are associated with DA.
METHODS
Sixty-two workers with DA confirmed by specific inhalation challenge (SIC) and 75 diisocyanate-exposed, SIC-negative workers were analyzed for SNPs associated with IL4RA, IL-13, and CD14 promoter genes.
RESULTS
No associations were found with individual SNPs and DA. When stratified according to specific diisocyanate exposure, a significant association was found between IL4RA (I50V) II and DA among individuals exposed to hexamethylene diisocyanate (HDI) (odds ratio [OR], 3.29; 95% confidence interval [CI], 1.33-8.14; P = .01) only. Similarly, the IL4RA (I50V) II and IL-13 (R110Q) RR combination was significantly associated with DA in HDI-exposed workers (OR, 4.13; 95% CI, 1.35-12.68; P = .01), as was the IL4RA (I50V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination IL4RA (I50V) II, IL-13 (R110Q) RR, and CD14 (C159T) CT (OR, 6.4; 95% CI, 1.57-26.12; P = .01).
CONCLUSIONS
Gene-environmental interactions may contribute to the pathogenesis of DA, and gene-gene interactions may modulate this relationship.
背景
二异氰酸酯哮喘（DA）影响2%至10%的接触工人，但这种疾病的发病机制仍不明确。
目的
确定白细胞介素4受体α（IL4RA）、白细胞介素-13（IL-13）和CD14启动子基因的特定单核苷酸多态性（SNP）是否与DA相关。
方法
对62名经特异性吸入激发试验（SIC）确诊为DA的工人和75名接触二异氰酸酯但SIC阴性的工人进行分析，检测与IL4RA、IL-13和CD14启动子基因相关的SNP。
结果
未发现单个SNP与DA之间存在关联。根据特定二异氰酸酯暴露情况进行分层时，仅在接触六亚甲基二异氰酸酯（HDI）的个体中发现IL4RA（I50V）II与DA之间存在显著关联（优势比[OR]，3.29；95%置信区间[CI]，1.33 - 8.14；P = 0.01）。同样，在接触HDI的工人中，IL4RA（I50V）II和IL-13（R110Q）RR组合与DA显著相关（OR，?4.13；95% CI，1.35 - 12.68；P = 0.01），IL4RA（I50V）II和CD14（C159T）CT基因型组合也与DA显著相关（OR，5.2；95% CI，1.82 - 14.88；P = 0.002），以及IL4RA（I50V）II、IL-13（R110Q）RR和CD14（C159T）CT的三联基因型组合与DA显著相关（OR，6.4；95% CI，1.57 - 26.12；P = 0.01）。
结论
基因 - 环境相互作用可能有助于DA的发病机制，基因 - 基因相互作用可能调节这种关系。
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