Diisocyanate asthma and gene-environment interactions with IL4RA, CD-14, and IL-13 genes.
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.
Bernstein
David I
DI
Department of Internal Medicine, Division of Immunology, University of Cincinnati Medical Center, Cincinnati, Ohio, USA.
Wang
Ning
N
Campo
Paloma
P
Chakraborty
Ranajit
R
Smith
Andrew
A
Cartier
André
A
Boulet
Louis-Philippe
LP
Malo
Jean-Luc
JL
Yucesoy
Berran
B
Luster
Michael
M
Tarlo
Susan M
SM
Hershey
Gurjit K Khurana
GK
D000368:Aged; D001249:Asthma / Q000139:chemically induced / Q000235:genetics*; D001985:Bronchial Provocation Tests; D016022:Case-Control Studies; D003485:Cyanates / Q000633:toxicity*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D018793:Interleukin-13 / Q000235:genetics*; D053662:Interleukin-4 Receptor alpha Subunit / Q000235:genetics*; D017953:Isocyanates / Q000633:toxicity*; D018950:Lipopolysaccharide Receptors / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009784:Occupational Diseases / Q000139:chemically induced / Q000235:genetics; D016273:Occupational Exposure; D020641:Polymorphism, Single Nucleotide
D003485:Cyanates; C504000:IL4R protein, human; D018793:Interleukin-13; D053662:Interleukin-4 Receptor alpha Subunit; D017953:Isocyanates; D018950:Lipopolysaccharide Receptors