RESUMO
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)
Assuntos
Humanos , Asma/genética , Rinite Alérgica Perene/genética , Cromossomos Humanos Par 12RESUMO
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
Blomia tropicalis is a mite of allergenic importance in tropical and subtropical areas. A clone (Bt11a) from a B. tropicalis complementary DNA library was expressed in lambda phage and analyzed by plaque radioimmunoassay. The recombinant allergen produced by this clone was bound by IgE in 16 of 32 sera from individuals with asthma with a positive RAST response and none of 3 control sera from healthy individuals with negative RAST response to B. tropicalis. The cDNA insert was amplified by polymerase chain reaction with use of universal primers. A 582-base-pair (bp) fragment was cloned into a pCR II vector. The complete sequence of both strands was determined by using T7, SP6, and internal primers. The sequence shows a 432 bp reading frame with a 34 bp 5' untranslated region and a 116 bp 3' untranslated region with a poly A tail. Analysis of the sequence suggests that it encodes a putative signal peptide of 20 residues and a 124-residue mature protein allergen of 14,206 Da. The nucleotide and the inferred amino acid sequences did not show homology to any known sequence. No potential N-linked glycosylation site was found. The recombinant protein appears to represent a major allergen of the mite B. tropicalis.
Assuntos
Alérgenos/genética , Asma/genética , DNA Complementar/genética , Imunoglobulina E/imunologia , Ácaros/genética , Adulto , Sequência de Aminoácidos , Animais , Sequência de Bases , Humanos , Imunoglobulina E/biossíntese , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Teste de Radioalergoadsorção , Proteínas Recombinantes/genética , Testes CutâneosRESUMO
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)
Assuntos
Ácaros , Asma , Anticorpos Anti-IdiotípicosRESUMO
The prevalence of specific IgE (RAST) to tropical house dust mite Blomia tropicalis (Bt) was studied in 126 related individuals with self-reported atopic asthma (AA) and/or self-reported allergic rhinitis (AR) and individuals with no reported atopic disease. RAST results were considered positive when a serum bound > 5 percent of the total counts (percent TCB) added; 17 (65.4 percent) AA were positive to Bt, 7 (29.2 percent) AR without AA were positive to Bt, and 16 (21.9 percent) individuals reporting no AA or AR were positive to Bt. Total serum IgE was significantly higher in individuals with self-reported AA (750 ng/ml) than in individuals reporting no AA (282 ng/ml; Student's t test, p = 0.02). There was no association between total serum IgE and self-reported AR. Additionally, total IgE was weakly correlated with RAST (Bt) for all individuals (r=0.349, p=0.001). Subjects with self-reported AA had a significantly higher mean percentage TCB (19 + 17) than individuals without self-reported AA (10 + 14; Student's test, p<0.05). This study suggests that sensitivity to Bt is common in individuals with atopic asthma living in Barbados (AU)