RESUMO
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).
Assuntos
Humanos , Asma/genética , Ligação Genética , Rinite Alérgica Perene/genética , BarbadosRESUMO
To identify genes potentially relevant in atopic asthma, we analyzed markers in chromosome 12q15-q24.1 for linkage to asthma and total serum IgE concentration. Sib-pair analyses of 10 markers in 345 full- and 219 half-sib pairs from 29 multiplex Afro-Caribbean families provided evidence for linkage to this region for both asthma and total serum IgE. Certain alleles at these loci showed significant evidence of transmission disequilibrium with both asthma and high IgE. Using 6 of these markers and 11 additional markers, evidence for linkage of total IgE to 12q was also found in 12 Caucasian Amish kindreds (24 nuclear families) by both sib-pair and transmission disequilibrium analyses. These findings suggest that the 12q15-q24.1 region may contain a gene(s) controlling asthma and the associated "high total IgE" trait.
Assuntos
Asma/genética , População Negra/genética , Cromossomos Humanos Par 12 , Ligação Genética , Imunoglobulina E/sangue , População Branca/genética , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Marcadores Genéticos , Humanos , Masculino , Pessoa de Meia-Idade , Núcleo Familiar , Índias OcidentaisRESUMO
To identify genes potentially relevant in atopic asthma, we analyzed markers in chromosome 12q15-q24.1 for linkage to asthma and total serum Ige concentration. Sib-pair analyses of 10 markers in 345 full- and 219 half-sib pairs from 29 multiplex Afro-Caribbean families provided evidence for linkage to his region for both asthma and total serum IgE. Certain alleles at these loci showed significant evidence of transmission disequilibrium with both asthma and high IgE. Using 6 of these markers and 11 additional markers, evidence for linkage of total IgE to 12q was also found in 12 Caucasian Amish kindreds (24 nuclear families) by both sib-pair and transmission disequilibrium analyses. These findings suggest that the 12q15-q24.1 region may contain a gene(s) contolling asthma and the associated high total IgE. trait.(AU)
Assuntos
Adolescente , Adulto , Idoso , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Asma/genética , /genética , Cromossomos Humanos Par 12 , Imunoglobulina E/sangue , Ligação Genética , /genética , Núcleo Familiar , Índias Ocidentais , Marcadores GenéticosRESUMO
Assessment of the epidemiology of asthma requires that the asthma phenotype be characterized. A study was conducted in Barbados among 24 families (n = 175 persons). The geometric mean serum total IgE (tIgE) was 559.8 ng/ml, and was significantly higher in asthmatic subjects (n = 88; means = 1352.1) than in non-asthmatic subjects (n = 87; means = 229.6; t-test, p < 0.001). Asthma subjects reported shortness of breath (80.7 percent), cough (77.3 percent), wheezing (72.7 percent). An index of asthma severity was created based on questionnaire data. Shortness of breath, cough and wheeze were similarly correlated with the index of severity; however, none of the symptoms were significantly correlated with tIgE. Similarly, tIgE was not correlated with the severity score of any of the individual variables that comprised the severity score. The findings in this study of Afro-Caribbean subjects living in a tropical setting concur with those of Caucasian subjects living in developed, temperate locales, whereby tIgE is a good means of classifying the presence or absence of asthma. The poor association between tIgE and severity of asthma and asthma symptoms warrants further investigation into the validation of the severity scale, but raises the question regarding the absence of a relationship between tIgE and asthma severity (AU)
Assuntos
Humanos , Masculino , Feminino , Asma/diagnóstico , Asma/epidemiologia , Imunoglobulina E/diagnóstico , Barbados/epidemiologiaRESUMO
The prevalence of specific IgE (RAST) to Blomia tropicalis (Bt) was evaluated for 64 individuals from four families residing in Barbados, with self-reported atopic asthma (AA) and/or self-reported allergic rhinitis (AR) or individuals with no reported atopic disease (NA). The presence of specific IgE antibodies that reacted with components of Chortoglyphus arcuatus (Ca), Dermatophagoides pteronyssinus (Dp) and Euroglyphus maynei (Em) was also evaluated; components from Ca, Dp and Em were separated by SDS-PAGE, transferred to nitrocellulose membranes and screened with sera from the 22 AAs, 17 ARs and 25 NAs. Total serum IgE was significantly higher in individuals with self-reported AA (logIgE = 977 ng/ml) than in individuals reporting no AA (logIgE = 323 ng/ml). There was a significant difference between the number of AAs who were Bt-positive according to RAST (68 percent) and the number of individuals without AA(p=0.002). IgE antibodies to Ch and Em were significantly higher in individuals with AA than in those without AA (p = 0.001 and p = 0.005, respectively), and there was a weak correlation between IgE antibodies to Dp and self-reported AA (p=0.05). A significant pattern of conversion of response to certain bands within families was observed (AU)