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

MOTIVATION: Local ancestry analysis of genotype data from recently admixed populations (e.g. Latinos, African Americans) provides key insights into population history and disease genetics. Although methods for local ancestry inference have been extensively validated in simulations (under many unrealistic assumptions), no empirical study of local ancestry accuracy in Latinos exists to date. Hence, interpreting findings that rely on local ancestry in Latinos is challenging. RESULTS: Here, we use 489 nuclear families from the mainland USA, Puerto Rico and Mexico in conjunction with 3204 unrelated Latinos from the Multiethnic Cohort study to provide the first empirical characterization of local ancestry inference accuracy in Latinos. Our approach for identifying errors does not rely on simulations but on the observation that local ancestry in families follows Mendelian inheritance. We measure the rate of local ancestry assignments that lead to Mendelian inconsistencies in local ancestry in trios (MILANC), which provides a lower bound on errors in the local ancestry estimates. We show that MILANC rates observed in simulations underestimate the rate observed in real data, and that MILANC varies substantially across the genome. Second, across a wide range of methods, we observe that loci with large deviations in local ancestry also show enrichment in MILANC rates. Therefore, local ancestry estimates at such loci should be interpreted with caution. Finally, we reconstruct ancestral haplotype panels to be used as reference panels in local ancestry inference and show that ancestry inference is significantly improved by incoroprating these reference panels. AVAILABILITY AND IMPLEMENTATION: We provide the reconstructed reference panels together with the maps of MILANC rates as a public resource for researchers analyzing local ancestry in Latinos at http://bogdanlab.pathology.ucla.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Assuntos

Hispânico ou Latino/genética , Viés , Estudos de Coortes , Família , Loci Gênicos , Genética Populacional/métodos , Genoma Humano , Estudo de Associação Genômica Ampla , Genótipo , Haplótipos , Humanos , Americanos Mexicanos , Porto Rico/etnologia , Estados Unidos/etnologia

RESUMO

MOTIVATION: It is becoming increasingly evident that the analysis of genotype data from recently admixed populations is providing important insights into medical genetics and population history. Such analyses have been used to identify novel disease loci, to understand recombination rate variation and to detect recent selection events. The utility of such studies crucially depends on accurate and unbiased estimation of the ancestry at every genomic locus in recently admixed populations. Although various methods have been proposed and shown to be extremely accurate in two-way admixtures (e.g. African Americans), only a few approaches have been proposed and thoroughly benchmarked on multi-way admixtures (e.g. Latino populations of the Americas). RESULTS: To address these challenges we introduce here methods for local ancestry inference which leverage the structure of linkage disequilibrium in the ancestral population (LAMP-LD), and incorporate the constraint of Mendelian segregation when inferring local ancestry in nuclear family trios (LAMP-HAP). Our algorithms uniquely combine hidden Markov models (HMMs) of haplotype diversity within a novel window-based framework to achieve superior accuracy as compared with published methods. Further, unlike previous methods, the structure of our HMM does not depend on the number of reference haplotypes but on a fixed constant, and it is thereby capable of utilizing large datasets while remaining highly efficient and robust to over-fitting. Through simulations and analysis of real data from 489 nuclear trio families from the mainland US, Puerto Rico and Mexico, we demonstrate that our methods achieve superior accuracy compared with published methods for local ancestry inference in Latinos.

Assuntos

Algoritmos , Genética Populacional , Hispânico ou Latino/genética , Fluxo Gênico , Genética Populacional/métodos , Haplótipos , Humanos , Indígenas Norte-Americanos/genética , Desequilíbrio de Ligação , Cadeias de Markov , México , Porto Rico , Estados Unidos , População Branca/genética

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: Although Mexicans and Puerto Ricans are jointly classified as "Hispanic/Latino," there are significant differences in asthma prevalence, severity, and mortality between the 2 groups. We sought to examine the possibility that population-specific genetic risks contribute to this disparity. OBJECTIVES: More than 100 candidate genes have been associated with asthma and replicated in an independent population, and 7 genome-wide association studies in asthma have been performed. We compared the pattern of replication of these associations in Puerto Ricans and Mexicans. METHODS: We genotyped Mexican and Puerto Rican trios using an Affymetrix 6.0 GeneChip and used a family-based analysis to test for genetic associations in 124 genes previously associated with asthma. RESULTS: We identified 32 single nucleotide polymorphisms (SNPs) in 17 genes associated with asthma in at least 1 of the 2 populations. Twenty-two of these SNPs in 11 genes were significantly associated with asthma in the combined population and showed no significant heterogeneity of association, whereas 5 SNPs were associated in only 1 population and showed statistically significant heterogeneity. In a gene-based approach 2 additional genes were associated with asthma in the combined population, and 3 additional genes displayed ethnic-specific associations with heterogeneity. CONCLUSIONS: Our results show that only a minority of genetic association studies replicate in our population of Mexican and Puerto Rican asthmatic subjects. Among SNPs that were successfully replicated, most showed no significant heterogeneity across populations. However, we identified several population-specific genetic associations.

Assuntos

Asma/genética , Predisposição Genética para Doença , Hispânico ou Latino/genética , Adolescente , Adulto , Asma/etnologia , Criança , Feminino , Hispânico ou Latino/etnologia , Humanos , Masculino , Americanos Mexicanos/genética , México/etnologia , Análise de Sequência com Séries de Oligonucleotídeos , Polimorfismo de Nucleotídeo Único , Porto Rico/etnologia , Fatores de Risco , Adulto Jovem

RESUMO

BACKGROUND: Salamanca, Mexico occupied fourth place nationally in contaminating emissions. The aim of the study was to determine the impact of air pollution on the frequency of pulmonary function alterations and respiratory symptoms in school-age children in a longitudinal repeated-measures study. METHODS: We recruited a cohort of 464 children from 6 to 14 years of age, from two schools differing in distance from the major stationary air pollution sources. Spirometry, respiratory symptoms and air pollutants (O3, SO2, NO, NO2, NOx, PM10,) were obtained for each season. Mixed models for continuous variables and multilevel logistic regression for respiratory symptoms were fitted taking into account seasonal variations in health effects according to air pollution levels. RESULTS: Abnormalities in lung function and frequency of respiratory symptoms were higher in the school closer to major stationary air pollution sources than in the distant school. However, in winter differences on health disappeared. The principal alteration in lung function was the obstructive type, which frequency was greater in those students with greater exposure (10.4% vs. 5.3%; OR = 1.95, 95% CI 1.0-3.7), followed by the mixed pattern also more frequent in the same students (4.1% vs. 0.9%; OR = 4.69, 95% CI, 1.0-21.1). PM10 levels were the most consistent factor with a negative relationship with FVC, FEV1 and PEF but with a positive relationship with FEV1/FVC coefficient according to its change per 3-month period. CONCLUSIONS: Students from the school closer to major stationary air pollution sources had in general more respiratory symptoms than those from the distant school. However, in winter air pollution was generalized in this city and differences in health disappeared. PM10 levels were the most consistent factor related to pulmonary function according, to its change per 3-month period.

Assuntos

Poluição do Ar/efeitos adversos , Pneumopatias Obstrutivas/epidemiologia , Pneumopatias Obstrutivas/fisiopatologia , Pulmão/fisiopatologia , Adolescente , Monóxido de Carbono/efeitos adversos , Criança , Estudos de Coortes , Feminino , Volume Expiratório Forçado/fisiologia , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , México/epidemiologia , Óxidos de Nitrogênio/efeitos adversos , Prevalência , Estações do Ano , Dióxido de Enxofre/efeitos adversos , Capacidade Vital/fisiologia

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

Many candidate genes have been studied for asthma, but replication has varied. Novel candidate genes have been identified for various complex diseases using genome-wide association studies (GWASs). We conducted a GWAS in 492 Mexican children with asthma, predominantly atopic by skin prick test, and their parents using the Illumina HumanHap 550 K BeadChip to identify novel genetic variation for childhood asthma. The 520,767 autosomal single nucleotide polymorphisms (SNPs) passing quality control were tested for association with childhood asthma using log-linear regression with a log-additive risk model. Eleven of the most significantly associated GWAS SNPs were tested for replication in an independent study of 177 Mexican case-parent trios with childhood-onset asthma and atopy using log-linear analysis. The chromosome 9q21.31 SNP rs2378383 (p = 7.10x10(-6) in the GWAS), located upstream of transducin-like enhancer of split 4 (TLE4), gave a p-value of 0.03 and the same direction and magnitude of association in the replication study (combined p = 6.79x10(-7)). Ancestry analysis on chromosome 9q supported an inverse association between the rs2378383 minor allele (G) and childhood asthma. This work identifies chromosome 9q21.31 as a novel susceptibility locus for childhood asthma in Mexicans. Further, analysis of genome-wide expression data in 51 human tissues from the Novartis Research Foundation showed that median GWAS significance levels for SNPs in genes expressed in the lung differed most significantly from genes not expressed in the lung when compared to 50 other tissues, supporting the biological plausibility of our overall GWAS findings and the multigenic etiology of childhood asthma.

Assuntos

Asma/genética , Cromossomos Humanos Par 9/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Adolescente , Adulto , Estudos de Casos e Controles , Criança , Feminino , Humanos , Masculino , México , Adulto Jovem

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

We set out to describe the pattern of lung function growth in Mexican students from 8-20 years of age, using internationally accepted equipment and methodology, and to compare it to values reported for Mexican-American children. Out of a total of 6,803 students from primary school to high school studied cross-sectionally in the Mexico City metropolitan area, we selected 4,009 asymptomatic, nonobese, nonsmoker subjects to generate spirometric prediction equations. We describe regression equations for the main spirometric variables (log transformed) based on age, height, and weight, and separated for males and females. Spirometric function in the population studied was above that predicted for European (Quanjer et al. [1987] Pediatr Pulmonol 19:135-142) or Mexican-American children, for the same age, height, and gender. On average, forced expiratory volume in 1 sec (FEV(1)) in Mexican children was 9.5% above that of Europeans (Quanjer et al. [1987] Pediatr Pulmonol 19:135-142), 14% and 5% above Hispanics reported by (Coultas et al. [1988] Am Rev Respir Dis 138:1386-1392) and (Hsu et al. [1979] J Pediatr 95:14-23), respectively, and 5% above Mexican-Americans from the third National Health and Nutrition Examination Survey study. Similarly, FVC was 8%, 14%, 8%, and 5.6% above the figures predicted by the same authors. The largest errors of prediction of foreign equations occurred in extremely tall or short subjects, and therefore a single proportional adjustment is unfeasible.

Assuntos

Americanos Mexicanos , Espirometria , Adolescente , Adulto , Estatura , Criança , Feminino , Volume Expiratório Forçado , Humanos , Masculino , México , Valores de Referência , Análise de Regressão , População Urbana , Capacidade Vital

RESUMO

Se presume que la prevalencia de reflujo gastroesofágico (RGE) en pacientes asmáticos es elevada, pero la frecuencia exacta se desconoce. En México no existen estudios que determinen la asociación entre RGE y asma. Los objetivos de este estudio son determinar la frecuencia de RGE en pacientes asmáticos mexicanos y conocer su relación con la gravedad del asma. Se estudiaron 50 pacientes con asma de inicio en la edad adulta según los criterios de los Institutos Nacionales de Salud de los E.U.A. La evaluación diagnóstica incluyó cuestionario de síntomas, espirometría, manometría, endoscopia y pH-metría esofágica de 24 horas. Veintitrés pacientes tenían asma leve (46 por ciento), 16 asma moderada (32 por ciento) y 11 asma grave (22 por ciento). Veintisiete pacientes (54 por ciento) presentaron pirosis y regurgitaciones dos o más veces por semanas, se detectó RGE patológico mediante pH-metría en 37 pacientes (74 por ciento) y sólo 7 casos (14 por ciento) tuvieron esofagitis en el estudio endoscopico. La pH-metría demostró RGE patológico en 13 pacientes con asma leve (57 por ciento), en 13 con asma moderadas (81 por ciento) y los 11 enfermos con asma grave (100 por ciento). La prevalencia de RGE en pacientes asmáticos mexicanos es elevada, principalmente en aquellos con asma grave. Sugerimos incluir la pH-metría esofágica en el estudio integral del paciente asmático

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Asma/complicações , Esôfago/fisiopatologia , Esofagoscopia , Concentração de Íons de Hidrogênio , Refluxo Gastroesofágico/diagnóstico , Refluxo Gastroesofágico/epidemiologia , Incidência , Manometria , México/epidemiologia , Inquéritos e Questionários

Assuntos

Asma/epidemiologia , Asma/prevenção & controle , Asma/terapia , Saúde Pública

RESUMO

Antecedentes. Se ha informado que existe una alta prevalencia de hernia hiatal y reflujo gastroesofágico en asmáticos, pero en México no contamos con estudios al respecto. La relación entre hernia hiatal y reflujo gastroesofágico en asmáticos no ha sido estudiada. Objetivos. 1) conocer la prevalencia de hernia hiatal en asmáticos, 2) comparar la prevalencia de hernia hiatal en asmáticos frente a sujetos no asmáticos, 3) establecer la posible asociación de la hernia hiatal con el reflujo gastroesofágico en enfermos asmáticos. Material y métodos. Se practicó endoscopia a pacientes asmáticos y no asmáticos para conocer y comparar la prevalencia de hernia hiatal. Con el fin de establecer la posible asociación entre asma y reflujo gastroesofágico se analizaron los resultados de un cuestionario de síntomas gastrointestinales, manometría esofágica y pH-metría en asmáticos con y sin hernia hiatal. Resultados. La prevalencia de hernia hiatal en asmáticos fue alta y significativa mayor a la detectada en no asmáticos (62 vs. 34 por ciento, p= 0.002). La frecuencia de síntomas típicos de reflujo gastroesofágico fue similar en asmáticos con y sin hernia hiatal (54 vs. 43 por ciento, p=0.3). La manometría detectó incompetencia del esfínter esofágico inferior en una proporción semejante de asmáticos con hernia hiatal (35 por ciento) y sin hernia hiatal (22 por ciento) (p=0.4). Se detectó reflujo gastroesofágico patológico mediante pH-metría en 81 por ciento de los asmáticos con hernia hiatal y en 65 por ciento de aquéllos sin hernia hiatal (p=0.1). Conclusiones. La prevalencia de hernia hiatal en asmáticos es elevada y mayor a la encontrada en sujetos no asmáticos. La presencia de hernia hiatal no se correlaciona con la detección de reflujo gastroesofágico patológico por pH-metría en este grupo de enfermos

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Asma , Hérnia Hiatal/diagnóstico , Hérnia Hiatal/epidemiologia , Refluxo Gastroesofágico/diagnóstico , Junção Esofagogástrica/fisiopatologia , Manometria , Inquéritos e Questionários