RESUMEN
As many as 80 percent of asthmatics have atopy and between 60 and 80 percent of allergic asthmatic have coexisting rhinitis. It has been proposed that asthma and allergic rhinitis are essentially the same inflammatory disease of human airways. Previously, we provided the first evidence for linkage of asthma and "high" total serum IgE concentration to chromosome 12q markers among families from Barbados and the US. To identify loci in this chromosome 12q region contributing to the distinct clinical phenotypes of asthma and allergic rhinitis, we conducted linkage analyses among 33 multiplex Barbadian families using densely-spaced microsatellite markers in the 12q14.3-q24.1 region. Maximal evidence for linkage to asthma and allergic rhinitis occurred at markers separated by 4.5 cM. D12S326 and D12S1052 = (NPL = 3.52, p = 0.001 and 1.72, p = 0.039, respectively), these two markers lie 9.13 cM downstream from IFNG. There was no evidence of linkage to either phenotype at markers flanking STAT6. These results suggest that a common gene on the long arm of chromosome 12 is important for both asthma and allergic rhinitis.(AU)
Asunto(s)
Humanos , Asma/genética , Rinitis Alérgica Perenne/genética , Cromosomas Humanos Par 12RESUMEN
Findings from numerous studies have demonstrated that there is a strong heritable component to asthma and atrophy, although the genetic pathophysiology of these traits is poorly understood. To identify loci in chromosome 12q1s-q24.1 contributing to asthma and asthma-associated traits, we conducted linkage analyses among 29 multiples Barbadian families. Sib-pair analysis of 10 polymorphic micro satellite markers in 345 full and 219 half-sib pairs from Barbados revealed evidence for linkage of certain markers with a gene(s) controlling asthma (D12S379,p=0.001; D12S311,p=0.010; D12S95,p=0.010; D12S360,p=0.018), allergic rhinitis (D12S1052,p=0.040; D12S311,p=0.005; D12S95,p0.021), total serum IgE concentration (D12S1052,p=0.016; D12S311,p=0.007; D12S360,p=0.013; D12S78,p=0.002), and specific IgE antibodies (Alec) to the storage mite Blomia tropicalis (Blot M; D12S311,p=0.006; D12S360,p=0.007; D12S78,p=0.003). Significant evidence of transmission disequilibrium was observe for certain alleles at these loci in addition to high multi allergen IgE Ab. These findings suggest that a gene(s) in the 12q 15-q24.1 region, which contains several candidate genes, including interferon-y (IFNG), is important for asthma and the associated traits of allergic rhinitis, "high" total IgE, and "high" specific IgE (AU).