Analysis of genetic heterogeneity of bronchial asthma as related to the age of onset

Earlier, the distribution of bronchial asthma (BA) morbidity with respect t o the age of onset (AO) in the Moscow population was found to be bimodal. T he distribution had two peaks (before and after 25 years of age) and a sign ificant (P < 0.001) minimum between them. Based on these data, genetic hete rogeneity of BA with respect to AO was hypothesized. The purpose of this st udy 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 to tal recurrent risk of BA were estimated in 1518 relatives of 815 BA proband s registered in several district outpatient clinics of Moscow. Based on the data obtained, phenotypic correlation between relatives and correlation by genotype between early-onset and late-onset BA cases (with AOs under and o ver 25 years, respectively) were estimated. It was demonstrated for the fir st time that the age distribution of BA morbidity in families of probands w as also bimodal, Moreover, when probands with early and late AOs were analy zed separately, proband relatives in each of the two groups exhibited these two peaks of morbidity. This suggests that BA that begins in adolescence a nd BA of adults are not genetically independent forms of the disease. This agrees with the data on the correlation by genotype between the "forms" wit h the early and late AOs, which does not significantly differ from 1. Howev er, the risk 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, patien ts with early-onset BA are more "loaded" genetically with respect to this d isease. Since the BA genetic heterogeneity connected with AO has not been c onfirmed in this study, it is assumed that the observed bimodal distributio n of BA morbidity with respect to age is accounted for by the effect of age itself, as a factor reflecting alternation of ontogenetic stages that affe ct susceptibility to BA so that the susceptibility threshold varies with ag e.