Abdelmotelb A M, Rose-Zerilli M J, Barton S J, Holgate S T, Walls A F, Holloway J W
Clinical and Experimental Sciences Unit, Faculty of Medicine, University of Southampton, Southampton, UK; Faculty of Medicine, Tanta University, Tanta, Egypt.
Clin Exp Allergy. 2014 Jun;44(6):822-30. doi: 10.1111/cea.12259.
Tryptase, a major secretory product of human mast cells has been implicated as a key mediator of allergic inflammation. Genetic variation in the tryptases is extensive, and α-tryptase, an allelic variant of the more extensively studied β-tryptase, is absent in substantial numbers of the general population. The degree to which α-tryptase expression may be associated with asthma has not been studied. We have investigated the α-tryptase gene copy number variation and its potential associations with phenotypes of asthma.
Caucasian families (n = 341) with at least two asthmatic siblings (n = 1350) were genotyped for the α-tryptase alleles, using high-resolution melting assays. Standards for the possible α-/β-tryptase ratios were constructed by cloning α-and β-tryptase PCR products to generate artificial templates. Association analysis of asthma affection status and related phenotypes [total and allergen-specific serum IgE, bronchial hyperresponsiveness to methacholine, forced expiratory volume in 1s (FEV1 ) and atopy and asthma severity scores] was undertaken using family-based association tests (FBAT).
Four consistent melting patterns for the α-tryptase genotype were identified with alleles carrying null, one or two copies of the α-tryptase allele. Possessing one copy of α-tryptase was significantly associated with lower serum levels of total and dust mite-specific IgE levels and higher FEV1 measurements, while two copies were related to higher serum concentrations of total and dust mite-specific IgE and greater atopy severity scores.
Associations of α-tryptase copy number with serum IgE levels, atopy scores and bronchial function may reflect roles for tryptases in regulating IgE production and other processes in asthma.
类胰蛋白酶是人类肥大细胞的一种主要分泌产物，被认为是过敏性炎症的关键介质。类胰蛋白酶的基因变异广泛，而α-类胰蛋白酶是研究更为广泛的β-类胰蛋白酶的一种等位基因变体，在相当数量的普通人群中不存在。α-类胰蛋白酶表达与哮喘的关联程度尚未得到研究。我们调查了α-类胰蛋白酶基因拷贝数变异及其与哮喘表型的潜在关联。
对至少有两个哮喘患儿（共1350名）的341个白种人家庭进行α-类胰蛋白酶等位基因基因分型，采用高分辨率熔解分析。通过克隆α-和β-类胰蛋白酶PCR产物以生成人工模板，构建可能的α-/β-类胰蛋白酶比率标准。使用基于家系的关联检验（FBAT）对哮喘患病状况及相关表型[总血清IgE和过敏原特异性血清IgE、对乙酰甲胆碱的支气管高反应性、1秒用力呼气量（FEV1）以及特应性和哮喘严重程度评分]进行关联分析。
确定了α-类胰蛋白酶基因型的四种一致熔解模式，其等位基因携带零拷贝、一拷贝或两拷贝的α-类胰蛋白酶等位基因。拥有一拷贝α-类胰蛋白酶与较低的总血清IgE水平和尘螨特异性IgE水平以及较高的FEV1测量值显著相关，而两拷贝则与较高的总血清IgE和尘螨特异性IgE浓度以及更高的特应性严重程度评分相关。
α-类胰蛋白酶拷贝数与血清IgE水平、特应性评分和支气管功能的关联可能反映了类胰蛋白酶在调节IgE产生及哮喘其他过程中的作用。
