RESUMO

We explored ancestry-related differences in the genetic architecture of whole-blood gene expression using whole-genome and RNA sequencing data from 2,733 African Americans, Puerto Ricans and Mexican Americans. We found that heritability of gene expression significantly increased with greater proportions of African genetic ancestry and decreased with higher proportions of Indigenous American ancestry, reflecting the relationship between heterozygosity and genetic variance. Among heritable protein-coding genes, the prevalence of ancestry-specific expression quantitative trait loci (anc-eQTLs) was 30% in African ancestry and 8% for Indigenous American ancestry segments. Most anc-eQTLs (89%) were driven by population differences in allele frequency. Transcriptome-wide association analyses of multi-ancestry summary statistics for 28 traits identified 79% more gene-trait associations using transcriptome prediction models trained in our admixed population than models trained using data from the Genotype-Tissue Expression project. Our study highlights the importance of measuring gene expression across large and ancestrally diverse populations for enabling new discoveries and reducing disparities.

Assuntos

Negro ou Afro-Americano , Hispânico ou Latino , Americanos Mexicanos , Humanos , Negro ou Afro-Americano/genética , Estudo de Associação Genômica Ampla , Hispânico ou Latino/genética , Americanos Mexicanos/genética , Fenótipo , Polimorfismo de Nucleotídeo Único , Transcriptoma

RESUMO

BACKGROUND: Little is known about the genetic determinants of severe asthma exacerbations. OBJECTIVES: We aimed to identify genetic variants associated with asthma hospitalizations. METHODS: We conducted a genome-wide association study of asthma hospitalizations in 34,167 white British adults with asthma, 1,658 of whom had at least 1 asthma-related hospitalization. This analysis was conducted by using logistic regression under an additive genetic model with adjustment for age, sex, body mass index, smoking status, and the first 5 principal components derived from genotypic data. We then analyzed data from 2 cohorts of Latino children and adolescents for replication and conducted quantitative trait locus and functional annotation analyses. RESULTS: At the chromosome 6p21.3 locus, the single-nucleotide polymorphism (SNP) rs56151658 (8 kb from the promoter of HLA-DQB1) was most significantly associated with asthma hospitalizations (for test allele A, odds ratio = 1.36 [95% CI = 1.22-1.52]; P = 3.11 × 10-8); 21 additional SNPs in this locus were associated with asthma hospitalizations at a P value less than 1 × 10-6. In the replication cohorts, multiple SNPs in strong linkage disequilibrium with rs56151658 were associated with severe asthma exacerbations at a P value of .01 or less in the same direction of association as in the discovery cohort. Three HLA genes (HLA-DQA2, HLA-DRB6, and HLA-DOB) were also shown to mediate the estimated effects of the SNPs associated with asthma hospitalizations through effects on gene expression in lung tissue. CONCLUSIONS: We identified strong candidate genes for asthma hospitalizations in adults in the region for class II HLA genes through genomic, quantitative trait locus, and summary data-based mendelian randomization analyses.

Assuntos

Asma/genética , Genótipo , Cadeias beta de HLA-DQ/genética , Hospitalização/estatística & dados numéricos , Adulto , Asma/epidemiologia , Estudos de Coortes , Feminino , Frequência do Gene , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Antígenos HLA-D/genética , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DR/genética , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Reino Unido/epidemiologia

RESUMO

American Thoracic Society guidelines recommend inhaled corticosteroid (ICS) therapy, plus a short-acting bronchodilator, in patients with persistent asthma. However, few prior studies have examined the efficacy of this combination in children of all racial/ethnic groups. We evaluated the association between ICS use and bronchodilator response (BDR) in three pediatric populations with persistent asthma (656 African American, 916 Puerto Rican, and 398 Mexican American children). The association was assessed using multivariable quantile regression. After adjusting for baseline forced expiratory volume in one second and use of controller medications, ICS use was significantly associated with increased BDR only among Mexican Americans (1.56%, P = 0.028) but not African Americans (0.49%, P = 0.426) or Puerto Ricans (0.16%, P = 0.813). Our results demonstrate that ICS augmentation is disproportionate across racial/ethnic groups, where improved BDR is observed in Mexican Americans only. This study highlights the complexities of treating asthma in children, and reinforces the importance of investigating the influence of race/ethnicity on pharmacological response.

Assuntos

Corticosteroides/uso terapêutico , Asma/tratamento farmacológico , Asma/etnologia , Broncodilatadores/uso terapêutico , Grupos Raciais/estatística & dados numéricos , Administração por Inalação , Adolescente , Corticosteroides/administração & dosagem , Negro ou Afro-Americano/estatística & dados numéricos , Broncodilatadores/farmacologia , Criança , Feminino , Volume Expiratório Forçado , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino , Americanos Mexicanos/estatística & dados numéricos , Porto Rico/etnologia , Estados Unidos/epidemiologia

RESUMO

RATIONALE: Adverse effects of exposures to ambient air pollution on lung function are well documented, but evidence in racial/ethnic minority children is lacking. OBJECTIVES: To assess the relationship between air pollution and lung function in minority children with asthma and possible modification by global genetic ancestry. METHODS: The study population consisted of 1,449 Latino and 519 African American children with asthma from five different geographical regions in the mainland United States and Puerto Rico. We examined five pollutants (particulate matter ≤10 µm and ≤2.5 µm in diameter, ozone, nitrogen dioxide, and sulfur dioxide), derived from participant residential history and ambient air monitoring data, and assessed over several time windows. We fit generalized additive models for associations between pollutant exposures and lung function parameters and tested for interaction terms between exposures and genetic ancestry. MEASUREMENTS AND MAIN RESULTS: A 5 µg/m(3) increase in average lifetime particulate matter less than or equal to 2.5 µm in diameter exposure was associated with a 7.7% decrease in FEV1 (95% confidence interval = -11.8 to -3.5%) in the overall study population. Global genetic ancestry did not appear to significantly modify these associations, but percent African ancestry was a significant predictor of lung function. CONCLUSIONS: Early-life particulate exposures were associated with reduced lung function in Latino and African American children with asthma. This is the first study to report an association between exposure to particulates and reduced lung function in minority children in which racial/ethnic status was measured by ancestry-informative markers.

Assuntos

Poluição do Ar/efeitos adversos , Asma/epidemiologia , Negro ou Afro-Americano/estatística & dados numéricos , Exposição Ambiental/estatística & dados numéricos , Hispânico ou Latino/estatística & dados numéricos , Pulmão/fisiopatologia , Grupos Minoritários/estatística & dados numéricos , Adolescente , Poluentes Atmosféricos/efeitos adversos , Asma/fisiopatologia , Criança , Feminino , Humanos , Masculino , Porto Rico/epidemiologia , Estados Unidos/epidemiologia

RESUMO

Mexico harbors great cultural and ethnic diversity, yet fine-scale patterns of human genome-wide variation from this region remain largely uncharacterized. We studied genomic variation within Mexico from over 1000 individuals representing 20 indigenous and 11 mestizo populations. We found striking genetic stratification among indigenous populations within Mexico at varying degrees of geographic isolation. Some groups were as differentiated as Europeans are from East Asians. Pre-Columbian genetic substructure is recapitulated in the indigenous ancestry of admixed mestizo individuals across the country. Furthermore, two independently phenotyped cohorts of Mexicans and Mexican Americans showed a significant association between subcontinental ancestry and lung function. Thus, accounting for fine-scale ancestry patterns is critical for medical and population genetic studies within Mexico, in Mexican-descent populations, and likely in many other populations worldwide.

Assuntos

Variação Genética , Indígenas Norte-Americanos/genética , Americanos Mexicanos/genética , População/genética , População Negra/genética , Genoma Humano , Humanos , México , População Branca/genética

RESUMO

RATIONALE: Air pollution is a known asthma trigger and has been associated with short-term asthma symptoms, airway inflammation, decreased lung function, and reduced response to asthma rescue medications. OBJECTIVES: To assess a causal relationship between air pollution and childhood asthma using data that address temporality by estimating air pollution exposures before the development of asthma and to establish the generalizability of the association by studying diverse racial/ethnic populations in different geographic regions. METHODS: This study included Latino (n = 3,343) and African American (n = 977) participants with and without asthma from five urban regions in the mainland United States and Puerto Rico. Residential history and data from local ambient air monitoring stations were used to estimate average annual exposure to five air pollutants: ozone, nitrogen dioxide (NO2), sulfur dioxide, particulate matter not greater than 10 µm in diameter, and particulate matter not greater than 2.5 µm in diameter. Within each region, we performed logistic regression to determine the relationship between early-life exposure to air pollutants and subsequent asthma diagnosis. A random-effects model was used to combine the region-specific effects and generate summary odds ratios for each pollutant. MEASUREMENTS AND MAIN RESULTS: After adjustment for confounders, a 5-ppb increase in average NO2 during the first year of life was associated with an odds ratio of 1.17 for physician-diagnosed asthma (95% confidence interval, 1.04-1.31). CONCLUSIONS: Early-life NO2 exposure is associated with childhood asthma in Latinos and African Americans. These results add to a growing body of evidence that traffic-related pollutants may be causally related to childhood asthma.

Assuntos

Poluentes Atmosféricos/efeitos adversos , Asma/etnologia , Negro ou Afro-Americano , Hispânico ou Latino , Grupos Minoritários , Material Particulado/efeitos adversos , Adolescente , Fatores Etários , Poluição do Ar , Asma/etiologia , Criança , Intervalos de Confiança , Monitoramento Ambiental/métodos , Feminino , Seguimentos , Humanos , Masculino , Razão de Chances , Porto Rico/epidemiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Estados Unidos/epidemiologia , População Urbana , Adulto Jovem

RESUMO

BACKGROUND: Atopy varies by ethnicity, even within Latino groups. This variation might be due to environmental, sociocultural, or genetic factors. OBJECTIVE: We sought to examine risk factors for atopy within a nationwide study of US Latino children with and without asthma. METHODS: Aeroallergen skin test responses were analyzed in 1830 US Latino subjects. Key determinants of atopy included country/region of origin, generation in the United States, acculturation, genetic ancestry, and site to which subjects migrated. Serial multivariate zero-inflated negative binomial regressions stratified by asthma status examined the association of each key determinant variable with the number of positive skin test responses. In addition, the independent effect of each key variable was determined by including all key variables in the final models. RESULTS: In baseline analyses African ancestry was associated with 3 times (95% CI, 1.62-5.57) as many positive skin test responses in asthmatic participants and 3.26 times (95% CI, 1.02-10.39) as many positive skin test responses in control participants. Generation and recruitment site were also associated with atopy in crude models. In final models adjusted for key variables, asthmatic patients of Puerto Rican (exp[ß] [95% CI], 1.31 [1.02-1.69]) and mixed (exp[ß] [95% CI], 1.27 [1.03-1.56]) ethnicity had a greater probability of positive skin test responses compared with Mexican asthmatic patients. Ancestry associations were abrogated by recruitment site but not region of origin. CONCLUSIONS: Puerto Rican ethnicity and mixed origin were associated with degree of atopy within US Latino children with asthma. African ancestry was not associated with degree of atopy after adjusting for recruitment site. Local environment variation, represented by site, was associated with degree of sensitization.

Assuntos

Asma/complicações , Asma/etnologia , Emigração e Imigração , Interação Gene-Ambiente , Hispânico ou Latino/estatística & dados numéricos , Hipersensibilidade Imediata/etnologia , Hipersensibilidade Imediata/genética , Adolescente , Alérgenos/imunologia , Asma/genética , Asma/imunologia , População Negra , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Hipersensibilidade Imediata/diagnóstico , Hipersensibilidade Imediata/imunologia , Masculino , Prevalência , Porto Rico , Fatores de Risco , Testes Cutâneos , Estados Unidos/epidemiologia

RESUMO

BACKGROUND: The effects of in utero tobacco smoke exposure on childhood respiratory health have been investigated, and outcomes have been inconsistent. OBJECTIVE: To determine if in utero tobacco smoke exposure is associated with childhood persistent asthma in Mexican, Puerto Rican, and black children. PATIENTS AND METHODS: There were 295 Mexican, Puerto Rican, and black asthmatic children, aged 8 to 16 years, who underwent spirometry, and clinical data were collected from the parents during a standardized interview. The effect of in utero tobacco smoke exposure on the development of persistent asthma and related clinical outcomes was evaluated by logistic regression. RESULTS: Children with persistent asthma had a higher odds of exposure to in utero tobacco smoke, but not current tobacco smoke, than did children with intermittent asthma (odds ratio [OR]: 3.57; P = .029). Tobacco smoke exposure from parents in the first 2 years of life did not alter this association. Furthermore, there were higher odds of in utero tobacco smoke exposure in children experiencing nocturnal symptoms (OR: 2.77; P = .048), daily asthma symptoms (OR: 2.73; P = .046), and emergency department visits (OR: 3.85; P = .015) within the year. CONCLUSIONS: Exposure to tobacco smoke in utero was significantly associated with persistent asthma among Mexican, Puerto Rican, and black children compared with those with intermittent asthma. These results suggest that smoking cessation during pregnancy may lead to a decrease in the incidence of persistent asthma in these populations.

Assuntos

Asma/etnologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Asma/epidemiologia , Criança , Feminino , Hispânico ou Latino/estatística & dados numéricos , Humanos , Modelos Logísticos , Bem-Estar Materno , Americanos Mexicanos/estatística & dados numéricos , Gravidez , Porto Rico/etnologia

RESUMO

BACKGROUND: Short-acting inhaled beta2-agonists such as albuterol are used for bronchodilation and are the mainstay of asthma treatment worldwide. There is significant variation in bronchodilator responsiveness to albuterol not only between individuals but also across racial/ethnic groups. The beta2-adrenergic receptor (beta2AR) is the target for beta2-agonist drugs. The enzyme, S-nitrosoglutathione reductase (GSNOR), which regulates levels of the endogenous bronchodilator S-nitrosoglutathione, has been shown to modulate the response to beta2-agonists. OBJECTIVE: We hypothesized that there are pharmacogenetic interactions between GSNOR and beta2AR gene variants that are associated with variable response to albuterol. METHODS: We performed family-based analyses to test for association between GSNOR gene variants and asthma and related phenotypes in 609 Puerto Rican and Mexican families with asthma. In addition, we tested these individuals for pharmacogenetic interaction between GSNOR and beta2AR gene variants and responsiveness to albuterol using linear regression. Cell transfection experiments were performed to test the potential effect of the GSNOR gene variants. RESULTS: Among Puerto Ricans, several GSNOR SNPs and a haplotype in the 3'UTR were significantly associated with increased risk for asthma and lower bronchodilator responsiveness (P=0.04-0.007). The GSNOR risk haplotype affects expression of GSNOR mRNA and protein, suggesting a gain of function. Furthermore, gene-gene interaction analysis provided evidence of pharmacogenetic interaction between GSNOR and beta2AR gene variants and the response to albuterol in Puerto Rican (P=0.03), Mexican (P=0.15) and combined Puerto Rican and Mexican asthmatics (P=0.003). Specifically, GSNOR+17059*beta2AR+46 genotype combinations (TG+GG*AG and TG+GG*GG) were associated with lower bronchodilator response. CONCLUSION: Genotyping of GSNOR and beta2AR genes may be useful in identifying Latino individuals, who might benefit from adjuvant therapy for refractory asthma.

Assuntos

Albuterol/farmacologia , Albuterol/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/farmacologia , Broncodilatadores/uso terapêutico , Albuterol/administração & dosagem , Aldeído Oxirredutases , Asma/genética , Asma/fisiopatologia , Broncodilatadores/administração & dosagem , Interações Medicamentosas/genética , Genes , Genótipo , Haplótipos , Hispânico ou Latino/genética , Humanos , Modelos Lineares , Americanos Mexicanos/genética , México , Oxirredutases/genética , Oxirredutases/farmacologia , Polimorfismo de Nucleotídeo Único , S-Nitrosoglutationa/farmacologia , S-Nitrosoglutationa/uso terapêutico

RESUMO

BACKGROUND: Ethnic-specific interactions between different asthma medications are not well described. OBJECTIVE: To determine whether the use of leukotriene modifiers is associated with the magnitude of bronchodilator responsiveness among Mexican American and Puerto Rican children with persistent asthma. METHODS: A cross-sectional study of 84 Mexican American and 192 Puerto Rican children, with persistent asthma who were aged 8 to 16 years. Within each group, bronchodilator responsiveness to albuterol, objectively assessed via spirometry, was compared between participants using leukotriene modifiers and those not using leukotriene modifiers. RESULTS: Leukotriene modifier use was associated with a clinically significant increase in percentage change in forced expiratory volume in 1 second of 11.8 (P < .001) in Puerto Rican children, but there was no significant change in percentage change in forced expiratory volume in 1 second (-3.2, P=.57) in Mexican American children. This finding persisted after controlling for the use of inhaled corticosteroids. In addition, among the Puerto Rican children, the association between leukotriene modifier use and augmented bronchodilator responsiveness was greatest in those younger than 12 years. CONCLUSIONS: Among children with persistent asthma, use of leukotriene modifiers is associated with augmented bronchodilator responsiveness to albuterol in Puerto Ricans, but not Mexican Americans. This ethnic-specific, drug-drug interaction highlights the need for the further understanding of asthma pharmacogenetics among children from different ethnic groups to improve asthma outcomes.

Assuntos

Asma/tratamento farmacológico , Asma/fisiopatologia , Broncodilatadores/administração & dosagem , Interações Medicamentosas , Antagonistas de Leucotrienos/administração & dosagem , Adolescente , Albuterol/administração & dosagem , Asma/etnologia , Criança , Estudos Transversais , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Hispânico ou Latino , Humanos , Masculino , Americanos Mexicanos , Resultado do Tratamento

RESUMO

OBJECTIVE: A recent admixture mapping analysis identified interleukin 6 (IL6) and IL6 receptor (IL6R) as candidate genes for inflammatory diseases. In the airways during allergic inflammation, IL6 signaling controls the production of proinflammatory and anti-inflammatory factors. In addition, albuterol, a commonly prescribed asthma therapy, has been shown to influence IL6 gene expression. Therefore, we reasoned that interactions between the IL6 and IL6R genes might be associated with bronchodilator drug responsiveness to albuterol in asthmatic patients. METHODS: Four functional IL6 single nucleotide polymorphisms (SNPs) and a nonsynonymous IL6R SNP were genotyped in 700 Mexican and Puerto Rican asthma families and in 443 African-American asthma cases and controls. Both family-based association tests and linear regression models were used to assess the association between individual SNPs and haplotypes with bronchodilator response. Gene-gene interactions were tested by using multiple linear regression analyses. RESULTS: No single SNP was consistently associated with drug response in all the three populations. However, on the gene level, we found a consistent IL6 and IL6R pharmacogenetic interaction in the three populations. This pharmacogenetic gene-gene interaction was contextual and dependent upon ancestry (racial background). This interaction resulted in higher drug response to albuterol in Latinos, but lower drug response in African-Americans. Herein, we show that there is an effect modification by ancestry on bronchodilator responsiveness to albuterol. CONCLUSION: Genetic variants in the IL6 and IL6R genes act synergistically to modify the bronchodilator drug responsiveness in asthma and this pharmacogenetic interaction is modified by the genetic ancestry.

Assuntos

Asma/tratamento farmacológico , Asma/genética , Broncodilatadores/uso terapêutico , Farmacogenética , Filogenia , Adolescente , Adulto , Negro ou Afro-Americano/genética , Indígena Americano ou Nativo do Alasca/genética , Estudos de Casos e Controles , Criança , Demografia , Feminino , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Humanos , Interleucina-6/genética , Modelos Lineares , Desequilíbrio de Ligação/genética , Masculino , Polimorfismo de Nucleotídeo Único/genética , Porto Rico/etnologia , Receptores de Interleucina-6/genética

RESUMO

RATIONALE: Independent replication of genetic associations in complex diseases, particularly in whole-genome association studies, is critical to confirm the association. OBJECTIVES: A whole-genome association study identified ORMDL3 as a promising candidate gene for asthma in white populations. Here, we attempted to confirm the role of ORMDL3 genetic variants in asthma in three ethnically diverse populations: Mexican, Puerto Rican, and African American. METHODS: We used family-based analyses to test for association between seven candidate single-nucleotide polymorphisms (SNPs) in and around the ORMDL3 gene and asthma and related phenotypes in 701 Puerto Rican and Mexican parent-child trios. We also evaluated these seven SNPs and an additional ORMDL3 SNP in 264 African American subjects with asthma and 176 healthy control subjects. MEASUREMENTS AND MAIN RESULTS: We found significant associations between two SNPs within ORMDL3 (rs4378650 and rs12603332) and asthma in Mexicans and African Americans (P = 0.028 and 0.001 for rs4378650 and P = 0.021 and 0.001 for rs12603332, respectively), and a trend toward association in Puerto Ricans (P = 0.076 and 0.080 for SNPs rs4378650 and rs12603332, respectively). These associations became stronger among Mexican and Puerto Rican subjects with asthma with IgE levels greater than 100 IU/ml. We did not find any association between ORMDL3 SNPs and baseline lung function or response to the bronchodilator albuterol. CONCLUSIONS: Our results confirm that the ORMDL3 locus is a risk factor for asthma in ethnically diverse populations. However, inconsistent SNP-level results suggest that further studies will be needed to determine the mechanism by which ORMDL3 predisposes to asthma.

Assuntos

Asma/etnologia , Asma/genética , Negro ou Afro-Americano/genética , Proteínas de Membrana/genética , Americanos Mexicanos/genética , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Volume Expiratório Forçado , Predisposição Genética para Doença/etnologia , Predisposição Genética para Doença/genética , Humanos , Masculino , Porto Rico/etnologia , Espirometria , Estados Unidos/epidemiologia

RESUMO

Socioeconomic and environmental differences do not fully explain differences in asthma prevalence, morbidity, and mortality among Puerto Ricans, African Americans, and Mexican Americans. Differences in response to albuterol may be a factor. We compared bronchodilator responsiveness between these three populations. All groups demonstrated below expected responsiveness. Puerto Ricans of all ages and African American children with moderate-to-severe asthma demonstrated the lowest responsiveness overall. Among subjects with moderate-to-severe asthma, children were even less likely than adults to show the expected bronchodilator response. We conclude that ethnic-specific differences in bronchodilator drug responsiveness exist between Mexicans, Puerto Ricans, and African Americans with asthma. This may be of importance in asthma management.

Assuntos

Albuterol/uso terapêutico , Asma/tratamento farmacológico , Asma/etnologia , Negro ou Afro-Americano , Broncodilatadores/uso terapêutico , Hispânico ou Latino , Americanos Mexicanos , Adolescente , Adulto , Asma/fisiopatologia , Criança , Feminino , Volume Expiratório Forçado/efeitos dos fármacos , Humanos , Masculino , México , Cidade de Nova Iorque , Porto Rico , São Francisco , Estatísticas não Paramétricas , Capacidade Vital/efeitos dos fármacos

RESUMO

BACKGROUND: High levels of IgE are associated with asthma. Whether higher levels of IgE are associated with more severe asthma is still unclear. OBJECTIVE: To determine whether IgE is associated with asthma severity among Latino and African American subjects with asthma. METHODS: We assessed lung function and asthma severity among African American, Mexican, and Puerto Rican patients with asthma with high IgE levels (> or =100 IU/mL; n = 492) and compared these values to those of patients with asthma with low IgE levels (<100 IU/mL; n = 247). We also examined IgE as a continuous variable among these groups. RESULTS: Patients with asthma with high IgE had a lower mean FEV(1) (87.6 +/- 17.1, percent of predicted) than patients with asthma with low IgE (91.5 +/- 17.0; P = .031). Regardless of race and ethnicity, baseline FEV(1), forced expiratory flow, and FEV(1)/forced vital capacity were lower among subjects with high IgE than among subjects with low IgE (P = .031, P < .0001, P = .0001, respectively). In addition, 54.7% of patients with asthma with high IgE had been previously hospitalized, compared with 44.1% of patients with asthma with low IgE (odds ratio, 1.33; 95% CI, 1.04-1.71). CONCLUSION: Higher IgE is associated with lower baseline lung function and more severe asthma among these populations. CLINICAL IMPLICATIONS: Among patients with asthma from 3 ethnically distinct groups, total IgE levels are inversely correlated with baseline lung function and asthma severity.

Assuntos

Asma/diagnóstico , Asma/etnologia , Imunoglobulina E/sangue , Adolescente , Adulto , Negro ou Afro-Americano , Criança , Humanos , México , Porto Rico

RESUMO

BACKGROUND: The prostanoid DP receptor (PTGDR) gene on chromosome 14q22.1 has been identified as an asthma susceptibility gene. A haplotype with decreased transcription factor binding and transcription efficiency was associated with decreased asthma susceptibility in African American and white subjects. The significance of PTGDR gene variants in asthma has yet to be determined in Latinos, the largest US minority population, nor has the association been replicated in other populations. OBJECTIVE: To determine the role of PTGDR gene variants in asthma susceptibility and asthma-related traits among the Mexican, Puerto Rican, and African American populations. METHODS: We determined whether single nucleotide polymorphisms (SNPs) and haplotypes in PTGDR were associated with asthma and asthma-related traits by family-based and cross-sectional cohort analyses in 336 Puerto Rican and 273 Mexican asthmatic trios and by case-control analysis among African American subjects with asthma and healthy controls (n = 352). RESULTS: We identified 13 SNPs in the PTGDR gene, and 6 were further analyzed. There was no significant association between PTGDR variants and asthma by family-based or case-control analyses. SNPs -441C and -197C and haplotype TTT showed marginal association with asthma-related traits in Mexican subjects. SNP -441 genotype TT (P = .05) and haplotype TTT (P = .02) were associated with increased IgE levels in African Americans. CONCLUSION: We conclude that the PTGDR gene is not a significant risk factor for asthma among Puerto Ricans, Mexicans, or African Americans. CLINICAL IMPLICATIONS: Asthma candidate genes provide insights to pathophysiology and potentially new therapeutic targets, although the PTGDR gene was not found to be a significant risk factor for asthma in 3 populations.

Assuntos

Asma/etnologia , Asma/genética , Negro ou Afro-Americano , Predisposição Genética para Doença , Hispânico ou Latino , Receptores Imunológicos/genética , Receptores de Prostaglandina/genética , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Cromossomos Humanos Par 14/genética , Estudos de Coortes , Estudos Transversais , Feminino , Haplótipos , Humanos , Masculino , Americanos Mexicanos , Polimorfismo de Nucleotídeo Único , Porto Rico/etnologia

RESUMO

BACKGROUND: In the United States, Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity, and mortality, respectively. Ethnic-specific differences in the response to drug treatment may contribute to differences in disease outcomes. Genetic variants at the beta(2)-adrenergic receptor (beta(2)AR) may modify asthma severity and albuterol responsiveness. We tested the association of beta(2)AR genotypes with asthma severity and bronchodilator response to albuterol in Puerto Ricans and Mexicans with asthma. METHODS: We used both family-based and cross-sectional tests of association with 8 beta(2)AR single nucleotide polymorphisms in 684 Puerto Rican and Mexican families. Regression analyses were used to determine the interaction between genotype, asthma severity, and bronchodilator drug responsiveness. RESULTS: Among Puerto Ricans with asthma, the arginine (Arg) 16 allele was associated with greater bronchodilator response using both family-based and cross-sectional tests (p = 0.00001-0.01). We found a strong interaction of baseline FEV(1) with the Arg16Glycine (Gly) polymorphism in predicting bronchodilator response. Among Puerto Ricans with asthma with baseline FEV(1) < 80% of predicted, but not in those with FEV(1) > 80%, there was a very strong association between the Arg16 genotype and greater bronchodilator responsiveness. No association was observed between Arg16Gly genotypes and drug responsiveness among Mexicans with asthma. CONCLUSIONS: Ethnic-specific pharmacogenetic differences exist between Arg16Gly genotypes, asthma severity, and bronchodilator response in Puerto Ricans and Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and drug responsiveness.

Assuntos

Albuterol/uso terapêutico , Asma/tratamento farmacológico , Broncodilatadores/uso terapêutico , Hispânico ou Latino/genética , Americanos Mexicanos/genética , Adolescente , Albuterol/farmacocinética , Alelos , Asma/genética , Broncodilatadores/farmacocinética , Criança , Feminino , Frequência do Gene , Genótipo , Haplótipos , Humanos , Masculino , México , Polimorfismo de Nucleotídeo Único , Porto Rico/etnologia , Receptores Adrenérgicos beta 2/genética , Receptores Adrenérgicos beta 2/metabolismo , Análise de Regressão , Testes de Função Respiratória , Estados Unidos

RESUMO

In the United States, Puerto Ricans and Mexicans have the highest and lowest asthma prevalence, morbidity, and mortality, respectively. To determine whether ethnicity-specific differences in therapeutic response, clinical response, and/or genetic factors contribute to differences in asthma outcomes, we compared asthma-related clinical characteristics among 684 Mexican and Puerto Rican individuals with asthma recruited from San Francisco, New York City, Puerto Rico, and Mexico City. Puerto Ricans with asthma had reduced lung function, greater morbidity, and longer asthma duration than did Mexicans with asthma. Bronchodilator responsiveness, measured as percentage change from baseline FEV1, was significantly lower among Puerto Ricans with asthma than among Mexicans with asthma. Puerto Ricans with asthma had on average 7.3% (95% confidence interval [CI], 4.6 to 9.9; p < 0.001) lower bronchodilator reversibility in FEV1, higher risk of an emergency department visit in the previous year (odds ratio, 2.63; 95% CI, 1.6 to 4.3; p < 0.001), and of previous hospitalization for asthma (odds ratio, 1.94; 95% CI, 1.2 to 3.2; p = 0.009) than Mexicans. Subgroup analysis corroborated that Puerto Ricans with asthma had more severe disease than did Mexicans on the basis of lung function measurements, responsiveness to beta2-adrenergic agonists, and health care use. We conclude that Puerto Ricans with asthma respond less to albuterol than do Mexicans with asthma. These findings underscore the need for additional research on racial/ethnic differences in asthma morbidity and response to therapy.

Assuntos

Asma/tratamento farmacológico , Asma/etnologia , Broncodilatadores/uso terapêutico , Hispânico ou Latino , Asma/diagnóstico , Testes de Provocação Brônquica , Estudos de Coortes , Feminino , Humanos , Modelos Lineares , Modelos Logísticos , Masculino , Americanos Mexicanos , Probabilidade , Prognóstico , Testes de Função Respiratória , Medição de Risco , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Resultado do Tratamento , Estados Unidos/epidemiologia

RESUMO

A recent study identified the ADAM33 gene as a promising candidate contributing to asthma. In Puerto Rican and Mexican populations, we have genotyped six single nucleotide polymorphisms (SNPs) that were used in the Genetics of Asthma in Latino Americans Study. We chose to study these two populations because in the United States, Puerto Ricans have the highest asthma prevalence, morbidity, and mortality and Mexicans the lowest. We used the transmission disequilibrium test to analyze associations between the ADAM33 gene variants and asthma, asthma severity, bronchodilator responsiveness, and total IgE levels using single SNPs, two to six SNP combinations, and specific haplotypes in 583 trios (proband with asthma and both biological parents). We also genotyped matched control samples to allow case-control analyses. None of the transmission disequilibrium test or case-control results showed significant association in either population. We found no evidence for association of single SNPs with asthma severity, bronchodilator response, or IgE levels in Mexicans or in the combined population. Two SNPs showed a modest association in Puerto Ricans, insignificant when the number of comparisons was taken into account. We conclude that the ADAM33 gene is not an important risk factor for asthma or for asthma-associated phenotypes in Mexicans or in Puerto Ricans.

Assuntos

Asma/genética , Hispânico ou Latino/genética , Metaloendopeptidases/genética , Americanos Mexicanos/genética , Polimorfismo de Nucleotídeo Único/genética , Proteínas ADAM , Adolescente , Asma/sangue , Asma/tratamento farmacológico , Broncodilatadores/administração & dosagem , Estudos de Casos e Controles , Criança , Feminino , Genótipo , Humanos , Imunoglobulina E/sangue , Masculino , Índice de Gravidade de Doença

RESUMO

Stridor, when present since birth, should alert the physician of the possibility of a major cause of airway obstruction. In some cases, it can be life-threatening if timely and adequate intervention is not performed. In this report we discuss an infant who presented with stridor since birth. It's clinical picture, diagnostic approach and management are reviewed. The use of fiberoptic bronchoscopy as the most important diagnostic tool in the evaluation of stridor is emphasized and prompt referral for proper evaluation is recommended

Assuntos

Feminino , Humanos , Recém-Nascido , Laringoestenose/congênito , Sons Respiratórios/etiologia , Anormalidades Múltiplas , Aorta Torácica/anormalidades , Artérias Carótidas/anormalidades , Broncoscopia , Cartilagem Cricoide/cirurgia , Cianose/etiologia , Laringoestenose/diagnóstico , Laringoestenose/cirurgia , Artéria Subclávia/anormalidades , Traqueostomia

RESUMO

La morbilidad y mortalidad por asma bronquial, aparentemente están aumentando. En nuestro esfuerzo continuado por estudiar el problema de ama bronquial en Puerto Rico descríbimos el perfil de un grupo de pacientes pediátricos admitidos durante un período de tres meses a un hospital de la comunidad. Es la intención que este sea el primer paso de un estudio más detallado dirigido hacia la evaluación de los factores de riesgo para hospitalización y la necesidad de tratamiento agudo para niños asmáticos de Puerto Rico. Hemos evaluado los expedientes de 119 admisiones con un diagnóstico de asma (Clave ICD-9 493) durante el perído comprendido entre el 22 de agosto de 1990 y el 21 de noviembre de 1990 (90 días). El análisis fué de naturaleza retrospectiva. Los datos recogidos de los expedientes comprendieron variables demográficos, de laboratorio y fisiológicos. Los resultados fueron comparables para ambos sexos. Las admisiones por asma bronquial representaron el 29% del total de admisiones con una estadía en el hospital de 4.07 + 1.09 días y edad de 4.62 + 4.29 años (media y desviación estándar). No se hicieron pruebas de función pulmonar para determinar la admisión. Se concluye que la necesidad de hospitalización del niño asmático en un hosptial de la comunidad se establece a base de la evaluación clínica. Las pruebas de función pulmonar incluyendo la medición del pico del flujo respiratorio no son factibles en la mayorìa de los niños que se admiten con asma bronquial por motivo de su edad. Se necesita desarrollar otros criterios para los niños asmáticos de menor edad

Assuntos

Adolescente , Criança , Pré-Escolar , Humanos , Asma/epidemiologia , Hospitalização , Prevalência , Porto Rico/epidemiologia , Testes de Função Respiratória , Estudos Retrospectivos , Fatores de Risco