Celedon J C, Silverman E K, Weiss S T, Wang B, Fang Z, Xu X
Channing Laboratory and Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Am J Respir Crit Care Med. 2000 Nov;162(5):1679-84. doi: 10.1164/ajrccm.162.5.2003007.
Phenotype assessment is a crucial issue in gene mapping studies of asthma. Recently, Panhuysen and coworkers proposed an algorithm to define the asthma phenotype in gene mapping family-based studies. We classified members of 2,756 Chinese families ascertained on the basis of the presence of two or more siblings and no more than one parent with asthma using a slightly modified version of the aforementioned algorithm. Among 4,097 Chinese parents, 404 (9.9%) were classified as having "definite asthma," 284 (6.9%) as "probable asthma," 1,193 (29.1%) as "unclassifiable obstructive airway disease, " 626 (15.3%) as "COPD," and 1,590 (38.8%) as "unaffected" (no obstructive airway disease). Among 6,424 Chinese offspring, 1,065 (16.6%) were classified as having "definite asthma," 820 (12.8%) as "probable asthma," 1,996 (31.1%) as "unclassifiable obstructive airway disease," 228 (3.5%) as "COPD," and 2,315 (36%) as "unaffected." The use of the algorithm proposed by Panhuysen and coworkers in a Chinese population with a high prevalence of smoking would result in the exclusion of subjects with asthma who smoke or who have severe airflow obstruction from linkage analysis, as well as in an inability to explore any potential interactions between genetic factors and cigarette smoking in the pathogenesis of asthma. In the absence of a "gold standard," definitions of asthma that incorporate a combination of respiratory symptoms, increased airway responsiveness or bronchodilator response, and a physician's diagnosis of asthma are reasonable. The choice of a particular diagnostic algorithm for family-based genetic studies of asthma should be made according to factors such as the prevalence of smoking in the study population. Genetic studies of intermediate phenotypes related to asthma, which are objectively defined and may be influenced by a smaller number of genes, continue to be of great importance.
表型评估是哮喘基因定位研究中的一个关键问题。最近，潘胡森及其同事提出了一种在基于家系的基因定位研究中定义哮喘表型的算法。我们使用上述算法的略微修改版本，对2756个中国家庭的成员进行了分类，这些家庭是根据有两个或更多兄弟姐妹且不超过一位患有哮喘的父母来确定的。在4097名中国父母中，404人（9.9%）被分类为患有“确诊哮喘”，284人（6.9%）为“可能哮喘”，1193人（29.1%）为“无法分类的阻塞性气道疾病”，626人（15.3%）为“慢性阻塞性肺疾病”，1590人（38.8%）为“未受影响”（无阻塞性气道疾病）。在6424名中国后代中，1065人（16.6%）被分类为患有“确诊哮喘”，820人（12.8%）为“可能哮喘”，1996人（31.1%）为“无法分类的阻塞性气道疾病”，228人（3.5%）为“慢性阻塞性肺疾病”，2315人（36%）为“未受影响”。在吸烟率高的中国人群中使用潘胡森及其同事提出的算法，将导致在连锁分析中排除吸烟或有严重气流阻塞的哮喘患者，并且无法探索哮喘发病机制中遗传因素与吸烟之间的任何潜在相互作用。在缺乏“金标准”的情况下，结合呼吸道症状、气道反应性增加或支气管扩张剂反应以及医生对哮喘的诊断来定义哮喘是合理的。对于基于家系的哮喘基因研究，应根据研究人群中的吸烟率等因素来选择特定的诊断算法。与哮喘相关的中间表型的基因研究仍然非常重要，这些表型是客观定义的，可能受较少数量基因的影响。
