β2-肾上腺素能受体基因单倍型在甲苯二异氰酸酯诱导哮喘中的可能作用。
Probable role of Beta 2-adrenergic receptor gene haplotype in toluene diisocyanate-induced asthma.
机构信息
Department of Allergy & Rheumatology, Ajou University School of Medicine, Suwon, Korea.
出版信息
Allergy Asthma Immunol Res. 2010 Oct;2(4):260-6. doi: 10.4168/aair.2010.2.4.260. Epub 2010 Sep 6.
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.
目的
β2-肾上腺素能受体的遗传多态性是与哮喘表型相关的主要因素。该多态性与甲苯二异氰酸酯（TDI）诱导的哮喘之间的关联尚未被研究。我们检查了 103 名 TDI 诱导的哮喘患者（TDI-OA）、60 名无症状暴露对照者（AEC）和 263 名未暴露的健康对照者（NC），以确定β2-肾上腺素能受体基因（ADRB2）多态性与 TDI 诱导的哮喘之间的可能关联。
方法
通过直接测序对 ADRB2 的单核苷酸多态性（SNP）进行基因分型。使用酶联免疫吸附试验测量血清特异性 IgE 和 IgG 水平。比较表型和临床患者参数。
结果
在 ADRB2 筛选过程中发现了 SNPs（-47 T>C、-20 T>C、Arg16Gly A>G、Gln27Glu C>G、Leu134Leu G>A、Arg175Arg C>A）（从-231 到 793 bp）。在任何六个 ADRB2 SNP 的等位基因和基因型频率方面均未发现显著差异。Arg16Gly A>G、Leu134Leu G>A 和 Arg175Arg C>A SNPs 以及单倍型 1[TTACGC]与 TDI 暴露者中 TDI-人血清白蛋白（HSA）缀合物的特异性 IgE 抗体显著相关（P<0.05）。具有 ADRB2 ht1/ht1 纯合子的暴露工人对 TDI-HSA 缀合物特异性 IgE 致敏率明显高于具有空 ht1 单倍型的工人（比值比，15.40；95%置信区间，1.81-131.06）。
结论
ADRB2 多态性可能影响 TDI 暴露工人对 TDI-HSA 缀合物的 IgE 特异性致敏。
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