Unit of Genetic Epidemiology and Bioinformatics, Dept of Epidemiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30.001, 9700 RB Groningen, The Netherlands.
Eur Respir J. 2010 Aug;36(2):261-8. doi: 10.1183/09031936.00123909. Epub 2010 Jan 14.
It is unclear to what extent the same set of environmental or genetic factors regulate objective intermediate asthma phenotypes. We examined heritabilities of these phenotypes and estimated their environmental and genetic overlap. We studied baseline lung function (forced expiratory volume in 1 s (FEV(1)), forced vital capacity (FVC) and FEV(1)/FVC), bronchial hyperresponsiveness, number of positive skin prick tests (SPT) to 11 allergens, serum total immunoglobulin (Ig)E, number of positive specific IgE tests to four allergens and eosinophil counts. 103 twin pairs were studied (46 monozygotic and 57 dizygotic; mean age: 22.5 yrs, range: 17.0-27.0 yrs). Univariate and bivariate genetic analyses were performed after adjustment for significant covariates. All intermediate asthma phenotypes showed significant heritabilities (47-83%). Most phenotypes were substantially correlated, which was mainly due to shared genetic factors. Pairs of phenotypes with the largest genetic correlations were specific IgE and SPT (0.98), and total IgE with specific IgE (0.87), with SPT (0.72), and with eosinophils (0.62). SPT showed significant environmental correlations with total IgE (0.65), specific IgE (0.70) and bronchial hyperresponsiveness (0.44). Genetic effects explain the majority of the variation in objective intermediate asthma phenotypes. Additionally, correlations between pairs of these traits are also mainly explained by genetic rather than environmental factors.
目前尚不清楚在何种程度上同样的环境或遗传因素调节客观的中间型哮喘表型。我们研究了这些表型的遗传性，并估计了它们的环境和遗传重叠。我们研究了基础肺功能（1 秒用力呼气量（FEV1）、用力肺活量（FVC）和 FEV1/FVC）、支气管高反应性、11 种过敏原的皮试阳性数（SPT）、血清总免疫球蛋白（Ig）E、4 种过敏原的特异性 IgE 阳性数和嗜酸性粒细胞计数。共研究了 103 对双胞胎（46 对同卵双生子和 57 对异卵双生子；平均年龄：22.5 岁，范围：17.0-27.0 岁）。在调整了显著协变量后，进行了单变量和双变量遗传分析。所有中间型哮喘表型均显示出显著的遗传性（47%-83%）。大多数表型具有显著相关性，主要是由于存在共同的遗传因素。具有最大遗传相关性的表型对是特异性 IgE 和 SPT（0.98），总 IgE 与特异性 IgE（0.87）、SPT（0.72）和嗜酸性粒细胞（0.62）。SPT 与总 IgE（0.65）、特异性 IgE（0.70）和支气管高反应性（0.44）具有显著的环境相关性。遗传因素解释了客观中间型哮喘表型的大部分变异。此外，这些性状之间的相关性也主要由遗传因素而不是环境因素解释。
