RESUMO
In Russian population of Siberia asthma is usually concomitant with high sensitization to indoor allergens (cat, dog and house dust mites), overproduction of total immunoglobulin E (IgE) and airway hyperreactivity. Definition of genes that predispose to development of various sub-components of the asthma phenotype is important for understanding of etiology of this disease. To map genes predisposing to asthma, we tested 21 microsatellite markers from candidate chromosomal regions in 136 Russian nuclear families with asthma from Siberia. We performed non-parametric analysis for linkage with asthma, total IgE, specific IgE to cat, dog, and dust mites, and spirometric indices (FEV1 (%) - percentage of predicted forced expiratory volume in 1s, FVC (%) - percentage of predicted forced vital capacity, and FEV1/FVC (%) - Tiffenau index). The most significant linkage was to the candidate region on chromosome 12. Locus controlling cat-specific IgE, which is the most abundant in asthma patients from Siberian population, mapped within the interval between 136 and 140 cM on chromosome 12q24.3, with the suggestive linkage at the marker D12S1611 (LOD=2.23, P=0.0007). Total IgE was also linked to this region (D12S1611 - LOD=1.12, P=0.012). FEV1 (%) exceeded LOD>1 threshold for significance with the same locus 12q24.3, but with the peak at a more proximal region at 111.87 cM (D12S338 - LOD=1.21, P=0.009). Some evidence of linkage (LOD>1.0) was also detected for asthma at 6p21.31 (D6S291) and total IgE at 13q14.2 (D13S165). These data indicate that the locus 12q24.3 is the most promising candidate for identification of asthma genes in Russian population of Siberia.
