Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14, and IL-13 genes

被引:42
作者
Bernstein, David I.
Wang, Ning
Campo, Paloma
Chakraborty, RanaJit
Smith, Andrew
Cartier, Andre
Boulet, Louis-Philippe
Malo, Jean-Luc
Yucesoy, Berran
Luster, Michael
Tarlo, Susan M.
Hershey, Gurjit K. Khurana
机构
[1] Childrens Hosp, Med Ctr, Dept Pediat, Div Allergy & Immunol, Cincinnati, OH 45229 USA
[2] Univ Cincinnati, Med Ctr, Dept Internal Med, Div Immunol, Cincinnati, OH 45267 USA
[3] Childrens Hosp, Med Ctr, Dept Pediat, Div Human Genet, Cincinnati, OH 45229 USA
[4] Univ Cincinnati, Med Ctr, Ctr Genome Informat, Dept Environm Hlth, Cincinnati, OH 45221 USA
[5] Hop Sacre Coeur, Montreal, PQ H4J 1C5, Canada
[6] Univ Laval, Hop Laval, Inst Cardiol & Pneumol, Ste Foy, PQ G1K 7P4, Canada
[7] NIOSH, Toxicol & Mol Biol Branch, Ctr Dis Control & Prevent, Morgantown, WV 26505 USA
[8] Univ Toronto, Gage Occupat & Environm Hlth Unit, Toronto, ON, Canada
关键词
D O I
10.1016/S1081-1206(10)60972-6
中图分类号
R392 [医学免疫学];
学科分类号
100102 [免疫学];
摘要
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 (150V) 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 (150V) 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 (150V) II and CD14 (C159T) CT genotype combination (OR, 5.2; 95% CI, 1.82-14.88; P = .002) and the triple genotype combination IL4RA (150V) 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.
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收藏
页码:800 / 806
页数:7
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