Allergy Asthma Immunol Res.  2010 Oct;2(4):260-266. 10.4168/aair.2010.2.4.260.

Probable Role of Beta 2-Adrenergic Receptor Gene Haplotype in Toluene Diisocyanate-Induced Asthma

• Ye YM
• Kang YM
• Kim SH
• Lee HY
• Kim CW
• Park CS
• Hong CS
• Park HS

• KMID: 2260387
• DOI: http://doi.org/10.4168/aair.2010.2.4.260

Abstract

PURPOSE
A genetic polymorphism of the beta 2-adrenergic receptor is a major factor associated with the asthmatic phenotype. The association of this polymorphism with toluene diisocyanate (TDI)-induced asthma has not been investigated. We examined 103 TDI-induced asthma patients (TDI-OA), 60 asymptomatic exposed controls (AEC), and 263 unexposed healthy controls (NC) in order to identify beta 2-adrenergic receptor gene (ADRB2) polymorphisms and the possible association with TDI-induced asthma.
METHODS
Single nucleotide polymorphisms (SNPs) of ADRB2 were genotyped by direct sequencing. Serum-specific IgE and IgG levels were measured using an enzyme-linked immunosorbent assay. Phenotypes and clinical patient parameters were compared.
RESULTS
SNPs were identified (-47 T>C, -20 T>C, Arg16Gly A>G, Gln27Glu C>G, Leu134Leu G>A, Arg175Arg C>A) during ADRB2 screening (from -231 to 793 bp). No significant differences in allelic and genotypic frequencies were noted for any of the six ADRB2 SNPs. The Arg16Gly A>G, Leu134Leu G>A, and Arg175Arg C>A SNPs and haplotype 1 [TTACGC] were significantly associated with specific IgE antibodies to the TDI-human serum albumin (HSA) conjugate in TDI-exposed subjects (P<0.05). Exposed workers with the ADRB2 ht1/ht1 homozygote had a significantly higher TDI-HSA conjugate-specific IgE sensitization rate than did those with the null ht1 haplotype (odds ratio, 15.40; 95% confidence interval, 1.81-131.06).
CONCLUSIONS
ADRB2 polymorphisms may affect IgE-specific sensitization to TDI-HSA conjugate in TDI-exposed workers.

Keyword

Isocyanate; asthma; beta2-adrenergic receptor; specific IgE; genetic susceptibility

MeSH Terms

Antibodies
Asthma
Enzyme-Linked Immunosorbent Assay
Genetic Predisposition to Disease
Haplotypes
Homozygote
Humans
Immunoglobulin E
Immunoglobulin G
Mass Screening
Phenotype
Polymorphism, Genetic
Polymorphism, Single Nucleotide
Serum Albumin
Toluene
Toluene 2,4-Diisocyanate
Antibodies
Immunoglobulin E
Immunoglobulin G
Serum Albumin
Toluene
Toluene 2,4-Diisocyanate

Figure

• 

  Figure Linkage disequilibrium plot of ADRB2 6 polymorphisms using the confidence bounds color scheme of Haploview 3.32. Dark grey, light grey, and white blocks indicate strong evidence for linkage disequilibrium, uninformative, and strong evidence for recombination, respectively.

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