Bouzigon E, Siroux V, Dizier M-H, Lemainque A, Pison C, Lathrop M, Kauffmann F, Demenais F, Pin I
INSERM U794, Tour Evry 2, 523 Place des Terrasses de l'Agora, 91034 Evry, France.
Eur Respir J. 2007 Aug;30(2):253-9. doi: 10.1183/09031936.00162206. Epub 2007 Apr 25.
There is ongoing debate as to how asthma should be defined in order to forward understanding of the underlying mechanisms. The aim of the present study was to build quantitative scores of asthma and asthma severity and to assess whether refinement of disease phenotypes can facilitate the identification of chromosomal regions harbouring susceptibility genes. A genome-wide linkage scan was conducted in 110 families with at least two asthmatic siblings (n = 508) from the French Epidemiological study on the Genetics and Environment of Asthma, bronchial hyperresponsiveness and atopy (EGEA). The phenotypes studied were an asthma severity score (assessed among asthmatics by combining clinical data and treatment), forced expiratory volume in one second (FEV(1)) and an asthma score (including both asthmatics and nonasthmatics and representing the whole disease spectrum). This analysis showed genome-wide suggestive evidence of linkage of the asthma score to 18p11, a novel region undetected in a previous screen of dichotomous asthma. There was potential linkage of 2p23 to asthma severity score and of three regions (1p36, 2q36 and 6q14) to FEV(1). Moreover, FEV(1) appeared to have no genetic determinant in common with asthma severity and asthma scores. Asthma and asthma severity quantitative scores revealed new regions of linkage and thus provide support for considering these phenotypes in future genetic studies.
关于如何定义哮喘以促进对潜在机制的理解，目前仍存在争议。本研究的目的是建立哮喘及哮喘严重程度的定量评分，并评估疾病表型的细化是否有助于识别携带易感基因的染色体区域。对来自法国哮喘、支气管高反应性和特应性的遗传与环境流行病学研究（EGEA）的110个家庭（n = 508）进行了全基因组连锁扫描，这些家庭中至少有两个患哮喘的兄弟姐妹。所研究的表型包括哮喘严重程度评分（通过结合临床数据和治疗情况在哮喘患者中进行评估）、一秒用力呼气容积（FEV(1)）和哮喘评分（包括哮喘患者和非哮喘患者，代表整个疾病谱）。该分析显示全基因组范围内哮喘评分与18p11存在提示性连锁证据，这是一个在先前二分法哮喘筛查中未检测到的新区域。2p23与哮喘严重程度评分存在潜在连锁，三个区域（1p36、2q36和6q14）与FEV(1)存在潜在连锁。此外，FEV(1)似乎与哮喘严重程度和哮喘评分没有共同的遗传决定因素。哮喘及哮喘严重程度的定量评分揭示了新的连锁区域，因此为在未来的遗传研究中考虑这些表型提供了支持。
