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Hui-Ju Tsai,
Nishat Shaikh,
Jennifer Y. Kho,
Natalie Battle,
Mariam Naqvi, Daniel Navarro,
Henry Matallana,
Craig M. Lilly,
Celeste S. Eng,
Gunjan Kumar,
Shannon Thyne,
H. George Watson,
Kelley Meade,
Michael LeNoir,
Shweta Choudhry,
Esteban G. Burchard,
from the Study of African Americans, Asthma, Genes Environments (SAGE
[show abstract]
[hide abstract]
ABSTRACT: β2-Adrenergic receptor (β2AR) gene polymorphisms have been reported to be associated with various asthma-related traits in different racial/ethnic populations. However, it is unknown whether β
2
AR genetic variants are associated with asthma in African Americans. In this study, we have examined whether there is association between β
2
AR genetic variants and asthma in African Americans. We have recruited 264 African American asthmatic subjects and 176 matched healthy controls participating in the Study of African Americans, Asthma, Genes and Environments (SAGE). We genotyped seven known and recently identified β
2
AR SNP variants, then tested genotype and haplotype association of asthma-related traits with the β
2
AR SNPs in our African American cohort with adjustment of confounding effect due to admixture background and environmental risk factors. We found a significant association of the SNP −47 (Arg-19Cys) polymorphism with ΔFEF25–75, a measure of bronchodilator drug responsiveness, in African American asthmatics after correction for multiple testing (P=0.001). We did not observe association of the SNP +46 (Arg16Gly) variant with asthma disease diagnosis and asthma-related phenotypes. In contrast to previous results between the Arg16Gly variant and traits related to bronchodilator responsiveness, our results indicate that the Arg-19Cys polymorphism in β upstream peptide may play an important role in bronchodilator drug responsiveness in African American subjects. Our findings highlight the importance of investigating genetic risk factors for asthma in different populations.
Human Genetics 04/2012; 119(5):547-557. · 5.07 Impact Factor
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Mariam Naqvi,
Haig Tcheurekdjian,
Julie A DeBoard,
L Keoki Williams, Daniel Navarro,
Richard A Castro,
Jose R Rodriguez-Santana,
Rocio Chapela,
H Geoffrey Watson,
Kelley Meade,
William Rodriguez-Cintron,
Michael LeNoir,
Shannon M Thyne,
Pedro C Avila,
Shweta Choudhry,
Esteban González Burchard
[show abstract]
[hide abstract]
ABSTRACT: National asthma guidelines recommend that patients with persistent asthma regularly use an inhaled corticosteroid (ICS) in addition to as-needed albuterol, yet recent debates question whether this combination is equally efficacious in all ethnicities.
To examine the effect of ICS use on bronchodilator responsiveness to albuterol in 3 different ethnic populations.
A cross-sectional study of 106 Mexican Americans, 246 Puerto Ricans, and 163 African Americans with physician-diagnosed persistent asthma. Asthma severity, ethnicity, and medication use were evaluated using spirometry and questionnaires. Percentage change in forced expiratory volume in 1 second (FEV) was compared in patients who used ICSs vs those who used a short-acting beta2-agonist as their only asthma medication.
Inhaled corticosteroid use was associated with improvements in the percentage change in FEV1 after albuterol administration in Mexican Americans (21.7%, P = .01) and Puerto Ricans (18.5%, P = .02) but not in African Americans (3.0%, P = .73).
Inhaled corticosteroid use is associated with augmented bronchodilator responsiveness to albuterol in Mexican Americans and Puerto Ricans, but not in African Americans, with persistent asthma. This underscores the need for an improved understanding of ethnic-specific drug-drug interactions, particularly in those subgroups experiencing the highest burden of asthma morbidity and mortality in the United States.
Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology 07/2008; 100(6):551-7. · 2.83 Impact Factor
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Mariam Naqvi,
Shannon Thyne,
Shweta Choudhry,
Hui-ju Tsai, Daniel Navarro,
Richard A Castro,
Sylvette Nazario,
Jose R Rodriguez-Santana,
Jesus Casal,
Alfonso Torres,
Rocio Chapela,
H Geoffrey Watson,
Kelley Meade,
Michael LeNoir,
Pedro C Avila,
William Rodriguez-Cintron,
Esteban González Burchard
[show abstract]
[hide abstract]
ABSTRACT: 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.
Journal of Asthma 11/2007; 44(8):639-48. · 1.52 Impact Factor
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Mariam Naqvi,
Shweta Choudhry,
Hui-Ju Tsai,
Shannon Thyne, Daniel Navarro,
Sylvette Nazario,
Jose R Rodriguez-Santana,
Jesus Casal,
Alfonso Torres,
Rocio Chapela,
H Geoffrey Watson,
Kelley Meade,
William Rodriguez-Cintron,
Michael Lenoir,
Pedro C Avila,
Esteban González Burchard
[show abstract]
[hide abstract]
ABSTRACT: High levels of IgE are associated with asthma. Whether higher levels of IgE are associated with more severe asthma is still unclear.
To determine whether IgE is associated with asthma severity among Latino and African American subjects with asthma.
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.
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).
Higher IgE is associated with lower baseline lung function and more severe asthma among these populations.
Among patients with asthma from 3 ethnically distinct groups, total IgE levels are inversely correlated with baseline lung function and asthma severity.
Journal of Allergy and Clinical Immunology 07/2007; 120(1):137-43. · 11.00 Impact Factor
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Yuhjung J Tsai,
Shweta Choudhry,
Jennifer Kho,
Kenneth Beckman,
Hui-Ju Tsai, Daniel Navarro,
Henry Matallana,
Richard A Castro,
Craig M Lilly,
Sylvette Nazario, [......],
Jesus Casal,
Alfonso Torres,
Jorge Salas,
Rocio Chapela,
H George Watson,
Kelley Meade,
Pedro C Avila,
William Rodriguez-Cintron,
Michael LeNoir,
Esteban González Burchard
[show abstract]
[hide abstract]
ABSTRACT: 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.
To determine the role of PTGDR gene variants in asthma susceptibility and asthma-related traits among the Mexican, Puerto Rican, and African American populations.
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).
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.
We conclude that the PTGDR gene is not a significant risk factor for asthma among Puerto Ricans, Mexicans, or African Americans.
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.
Journal of Allergy and Clinical Immunology 01/2007; 118(6):1242-8. · 11.00 Impact Factor
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Hui-Ju Tsai,
Nishat Shaikh,
Jennifer Y Kho,
Natalie Battle,
Mariam Naqvi, Daniel Navarro,
Henry Matallana,
Craig M Lilly,
Celeste S Eng,
Gunjan Kumar,
Shannon Thyne,
H George Watson,
Kelley Meade,
Michael LeNoir,
Shweta Choudhry,
Esteban G Burchard
[show abstract]
[hide abstract]
ABSTRACT: Beta2-adrenergic receptor (beta2AR) gene polymorphisms have been reported to be associated with various asthma-related traits in different racial/ethnic populations. However, it is unknown whether beta2AR genetic variants are associated with asthma in African Americans. In this study, we have examined whether there is association between beta2AR genetic variants and asthma in African Americans. We have recruited 264 African American asthmatic subjects and 176 matched healthy controls participating in the Study of African Americans, Asthma, Genes and Environments (SAGE). We genotyped seven known and recently identified beta2AR SNP variants, then tested genotype and haplotype association of asthma-related traits with the beta2AR SNPs in our African American cohort with adjustment of confounding effect due to admixture background and environmental risk factors. We found a significant association of the SNP -47 (Arg-19Cys) polymorphism with DeltaFEF(25-75), a measure of bronchodilator drug responsiveness, in African American asthmatics after correction for multiple testing (P = 0.001). We did not observe association of the SNP +46 (Arg16Gly) variant with asthma disease diagnosis and asthma-related phenotypes. In contrast to previous results between the Arg16Gly variant and traits related to bronchodilator responsiveness, our results indicate that the Arg-19Cys polymorphism in beta upstream peptide may play an important role in bronchodilator drug responsiveness in African American subjects. Our findings highlight the importance of investigating genetic risk factors for asthma in different populations.
Human Genetics 07/2006; 119(5):547-57. · 5.07 Impact Factor
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Hui-Ju Tsai,
Jennifer Y Kho,
Nishat Shaikh,
Shweta Choudhry,
Mariam Naqvi, Daniel Navarro,
Henry Matallana,
Richard Castro,
Craig M Lilly,
H George Watson,
Kelley Meade,
Michael Lenoir,
Shannon Thyne,
Elad Ziv,
Esteban González Burchard
[show abstract]
[hide abstract]
ABSTRACT: Case-control genetic association studies in admixed populations are known to be susceptible to genetic confounding due to population stratification. The transmission/disequilibrium test (TDT) approach can avoid this problem. However, the TDT is expensive and impractical for late-onset diseases. Case-control study designs, in which, cases and controls are matched by admixture, can be an appealing and a suitable alternative for genetic association studies in admixed populations. In this study, we applied this matching strategy when recruiting our African American participants in the Study of African American, Asthma, Genes and Environments. Group admixture in this cohort consists of 83% African ancestry and 17% European ancestry, which was consistent with reports from other studies. By carrying out several complementary analyses, our results show that there is a substructure in the cohort, but that the admixture distributions are almost identical in cases and controls, and also in cases only. We performed association tests for asthma-related traits with ancestry, and only found that FEV(1), a measure for baseline pulmonary function, was associated with ancestry after adjusting for socio-economic and environmental risk factors (P=0.01). We did not observe an excess of type I error rate in our association tests for ancestry informative markers and asthma-related phenotypes when ancestry was not adjusted in the analyses. Furthermore, using the association tests between genetic variants in a known asthma candidate gene, beta(2) adrenergic receptor (beta(2)AR) and DeltaFEF(25-75), an asthma-related phenotype, as an example, we demonstrated population stratification was not a confounder in our genetic association. Our present work demonstrates that admixture-matched case-control strategies can efficiently control population stratification confounding in admixed populations.
Human Genetics 02/2006; 118(5):626-39. · 5.07 Impact Factor
