Ukraintseva S V, Sergeev A S
Medical Genetic Research Center, Russian Academy of Medical Sciences, Moscow, Russia.
Genetika. 2000 Feb;36(2):266-70.
Earlier, the distribution of bronchial asthma (BA) morbidity with respect to the age of onset (AO) in the Moscow population was found to be bimodal. The distribution had two peaks (before and after 25 years of age) and a significant (P < 0.001) minimum between them. Based on these data, genetic heterogeneity of BA with respect to AO was hypothesized. The purpose of this study was to test this hypothesis via analysis of BA morbidity in families of probands with different AOs. The BA morbidity at different ages and the total recurrent risk of BA were estimated in 1518 relatives of 815 BA probands registered in several district outpatient clinics of Moscow. Based on the data obtained, phenotypic between relatives and correlation by genotype between early-onset and late-onset BA cases (with AOs under and over 25 years, respectively) were estimated. It was demonstrated for the first time that the age distribution of BA morbidity in families of probands was also bimodal. Moreover, when probands with early and late AOs were analyzed separately, proband relatives in each of the two groups exhibited these two peaks of morbidity. This suggests that BA that begins in adolescence and BA of adults are not genetically independent forms of the disease. This agrees with the data on the correlation by genotype between the "forms" with the early and late AOs, which does not significantly differ from 1. However, the prevalence of BA was higher in relatives of those probands who developed BA under the age of 25 compared to relatives of those who developed BA over the age of 25 (11.28 and 7.31%, respectively; P < 0.05). Therefore, patients with early-onset BA are more "burdened" genetically with respect to this disease. Since the BA genetic heterogeneity connected with AO has not been confirmed in this study, it is assumed that the observed bimodal distribution of BA morbidity with respect to age is accounted for by the effect of age itself. In other words, it is hypothesized that ontogenetic factors affect susceptibility to BA so that the susceptibility threshold varies with age.
此前，研究发现莫斯科人群中支气管哮喘（BA）发病率随发病年龄（AO）的分布呈双峰模式。该分布有两个峰值（25岁之前和之后），且两者之间存在显著的最小值（P < 0.001）。基于这些数据，推测BA在AO方面存在遗传异质性。本研究的目的是通过分析不同AO的先证者家庭中的BA发病率来验证这一假设。对莫斯科几家地区门诊诊所登记的815名BA先证者的1518名亲属的不同年龄段BA发病率及BA的总复发风险进行了估计。根据所得数据，估计了亲属之间的表型以及早发型和晚发型BA病例（AO分别在25岁以下和以上）之间的基因型相关性。首次证明先证者家庭中BA发病率的年龄分布也是双峰的。此外，分别分析早发和晚发AO的先证者时，两组中的先证者亲属均呈现出这两个发病峰值。这表明青春期开始的BA和成人BA在遗传上并非独立的疾病形式。这与早发和晚发AO的“形式”之间基因型相关性的数据一致，该相关性与1无显著差异。然而，25岁以下患BA的先证者亲属中BA的患病率高于25岁以上患BA的先证者亲属（分别为11.28%和7.31%；P < 0.05）。因此，早发型BA患者在该疾病的遗传方面负担更重。由于本研究未证实与AO相关的BA遗传异质性，推测观察到的BA发病率随年龄的双峰分布是由年龄本身的影响所致。换句话说，推测个体发育因素会影响对BA的易感性，从而使易感性阈值随年龄变化。
