D'amato M, Vitiani L R, Petrelli G, Ferrigno L, di Pietro A, Trezza R, Matricardi P M
Department of Immunobiology, Institute of Cell Biology-CNR; Laboratorio Epidemiologia e Biostatistica, Istituto Superiore di Sanità, Rome, Italy.
Am J Respir Crit Care Med. 1998 Dec;158(6):1968-73. doi: 10.1164/ajrccm.158.6.9804126.
Bronchial hyperresponsiveness (BHR) is a hallmark of asthma and represents a strong risk factor for the disease. However, not all asthmatics have BHR and it can be observed in normal subjects too, probably because of genetic predisposition. Increasing attention is being focused on the beta2-adrenoceptor gene (ADRB2), whose genetic variability at amino acids 16 and 27 has been shown to correlate with some clinical features of asthma, including airways reactivity. To verify whether ADRB2 gene polymorphisms can influence BHR at a broader level, we studied a large, highly homogeneous sample of individuals sharing race, gender, age, and current living environment. BHR was strictly defined as a constant positive response to serial methacholine challenge tests and an improved definition of genetic variability at the ADRB2 locus was used, by identifying the haplotypic combinations of polymorphisms 16 and 27. We observed that the ADRB2 haplotype with a Gly at position 16 and a Gln at position 27 is associated with BHR in our sample. The association persisted also after correction for potentially confounding variables such as specific and total IgE levels. This observation suggests therefore that ADRB2 gene can confer genetic susceptibility to BHR, rather than having only a disease-modifying effect in asthma.
支气管高反应性（BHR）是哮喘的一个标志，也是该疾病的一个重要危险因素。然而，并非所有哮喘患者都有BHR，正常受试者也可能出现BHR，这可能是由于遗传易感性。人们越来越关注β2肾上腺素能受体基因（ADRB2），其第16和27位氨基酸的基因变异性已被证明与哮喘的一些临床特征相关，包括气道反应性。为了验证ADRB2基因多态性是否能在更广泛的层面上影响BHR，我们研究了一个种族、性别、年龄和当前生活环境高度一致的大样本个体。BHR被严格定义为对连续的乙酰甲胆碱激发试验持续呈阳性反应，并通过识别第16和27位多态性的单倍型组合，对ADRB2基因座的基因变异性进行了更完善的定义。我们观察到，在我们的样本中，第16位为甘氨酸（Gly）且第27位为谷氨酰胺（Gln）的ADRB2单倍型与BHR相关。在对潜在的混杂变量（如特异性和总IgE水平）进行校正后，这种相关性仍然存在。因此，这一观察结果表明，ADRB2基因可赋予对BHR的遗传易感性，而不仅仅是对哮喘具有疾病修饰作用。
