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Haplotypes of IL-4 receptor and CD14 genetic polymorphisms are markers of susceptibility for diisocyanate asthma.

Authors
Bernstein-DI; Cartier-A; Wanner-M; Cote-J; Boulet-LP; Tarlo-S; Wang-N; Chakraborty-R; Hershey-GK
Source
Am J Respir Crit Care Med 2003 Apr; 167(7):A580
NIOSHTIC No.
20023070
Abstract
Diisocyanate asthma (DA) is associated with specific HLA-DQ alleles, glutathione-s-transferase and N-acetyltransferase genotypes. We evaluated polymorphisms for IL-4 receptor alpha (IL-4Rx), a common component of IL-4 and IL-13 receptors, IL-13, and CD14, a key constituent of the toll receptor complex. Studies were conducted in 18 workers with DA confirmed by inhalation challenge (DA+) and in 30 challenge negative (DA-) workers. Single nucleotide polymorphisms (snp) for IL-4Ralpha (Ile75Val, Glu400Ala, Glu 576 Arg or Q576R, Cys431Arg), IL-13 (R130Q) and CD14 (C159T) were analyzed to elucidate disease-associated genotypes. No associations were detected between DA and individual alleles. However, combinations of snps in the IL-4Ralpha and CD14 genes were found to be significantly associated with DA. The frequency of the IC haplotype (shared between I75V and C159T) was 0.44 in DA + workers vs. 023 among DA- subjects (p=0.04). The QC haplotype frequency (Q576R, C159T) of 0.667 in the DA + group was more frequent (0.425) than in the DA- groups (p=0.03). Furthermore, the frequency of IQC haplotype (l75V, Q576R, C159T) was 0.44 in DA + workers vs. 0.217 in the DA - group (p=0.04). The IC, QC and IQC haplotypes are significantly associated with the DA phenotype. Although the functional significance of these findings is uncertain, these haplotypes could be susceptibility markers for DA and may be useful aids in the diagnosis of DA.
Keywords
Pulmonary-system-disorders; Bronchial-asthma; Respiratory-system-disorders; Humans; Genotoxic-effects
CODEN
AJCMED
Publication Date
20030401
Document Type
Abstract; Conference/Symposia Proceedings
Funding Amount
1343329
Funding Type
Grant
Fiscal Year
2003
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-R01-OH-003519
Issue of Publication
7
ISSN
1073-449X
Priority Area
Disease and Injury: Asthma and Chronic Obstructive Pulmonary Disease
Source Name
American Journal of Respiratory and Critical Care Medicine, 2003 International Conference, The American Thoracic Society, Seattle, WA, May 16-21, 2003
State
OH
Performing Organization
University of Cincinnati, Cincinnati, OH
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