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Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects.

ABSTRACT: Inhaled corticosteroids (ICSs) are the preferred treatment for achieving asthma control. However, little is known regarding the factors contributing to treatment response and whether treatment response differs by population group.We sought to assess behavioral, sociodemographic, and genetic factors related to ICS response among African American and European American subjects with asthma.Study participants were part of the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE). The analytic sample included asthmatic subjects aged 12 to 56 years with greater than 12% bronchodilator reversibility and percent predicted FEV1 of between 40% and 90%. Participants received 6 weeks of inhaled beclomethasone dipropionate. The primary measure of ICS response was a change in Asthma Control Test (ACT) score; the secondary measure was a change in prebronchodilator FEV1. Adherence was measured with electronic monitors. Genetic ancestry was estimated for African American participants by using genome-wide genotype data.There were 339 study participants; 242 self-identified as African American and 97 as European American. Baseline ACT score, percent predicted FEV1, degree of bronchodilator response, and ICS adherence were significantly associated with ICS response. A baseline ACT score of 19 or less was useful in identifying those who would respond, as evidenced by the significant dose-response relationship with ICS adherence. Neither self-reported race-ethnicity among all participants nor proportion of African ancestry among African American participants was associated with ICS responsiveness.Our findings suggest that baseline lung function measures and self-reported asthma control predict ICS response, whereas self-reported race-ethnicity and genetic ancestry do not.

SUBMITTER: Wells KE

PROVIDER: S-EPMC5313277 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects.

Wells Karen E KE Cajigal Sonia S Peterson Edward L EL Ahmedani Brian K BK Kumar Rajesh R Lanfear David E DE Burchard Esteban G EG Williams L Keoki LK

The Journal of allergy and clinical immunology 20160322 5

<h4>Background</h4>Inhaled corticosteroids (ICSs) are the preferred treatment for achieving asthma control. However, little is known regarding the factors contributing to treatment response and whether treatment response differs by population group.<h4>Objective</h4>We sought to assess behavioral, sociodemographic, and genetic factors related to ICS response among African American and European American subjects with asthma.<h4>Methods</h4>Study participants were part of the Study of Asthma Pheno ...[more]

PMID: 27016472

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Project description:Background and purposeInhaled corticosteroids (ICS) are the cornerstone of asthma pharmacotherapy and, acting via the glucocorticoid receptor (GR), reduce inflammatory gene expression. While this is often attributed to a direct inhibitory effect of the GR on inflammatory gene transcription, corticosteroids also induce the expression of anti-inflammatory genes in vitro. As there are no data to support this effect in asthmatic subjects taking ICS, we have assessed whether ICS induce anti-inflammatory gene expression in subjects with atopic asthma.Experimental approachBronchial biopsies from allergen-challenged atopic asthmatic subjects taking inhaled budesonide or placebo were subjected to gene expression analysis using real-time reverse transcriptase-PCR for the corticosteroid-inducible genes (official gene symbols with aliases in parentheses): TSC22D3 [glucocorticoid-induced leucine zipper (GILZ)], dual-specificity phosphatase-1 (MAPK phosphatase-1), both anti-inflammatory effectors, and FKBP5 [FK506-binding protein 51 (FKBP51)], a regulator of GR function. Cultured pulmonary epithelial and smooth muscle cells were also treated with corticosteroids before gene expression analysis.Key resultsCompared with placebo, GILZ and FKBP51 mRNA expression was significantly elevated in budesonide-treated subjects. Budesonide also increased GILZ expression in human epithelial and smooth muscle cells in culture. Immunostaining of bronchial biopsies revealed GILZ expression in the airways epithelium and smooth muscle of asthmatic subjects.Conclusions and implicationsExpression of the corticosteroid-induced genes, GILZ and FKBP51, is up-regulated in the airways of allergen-challenged asthmatic subjects taking inhaled budesonide. Consequently, the biological effects of corticosteroid-induced genes should be considered when assessing the actions of ICS. Treatment modalities that increase or decrease GR-dependent transcription may correspondingly affect corticosteroid efficacy.

Project description:BackgroundFamily history and African-American race are important risk factors for both prostate cancer (CaP) incidence and aggressiveness. When studying complex diseases such as CaP that have a heritable component, chances of finding true disease susceptibility alleles can be increased by accounting for genetic ancestry within the population investigated. Race, ethnicity and ancestry were studied in a geographically diverse cohort of men with newly diagnosed CaP.MethodsIndividual ancestry (IA) was estimated in the population-based North Carolina and Louisiana Prostate Cancer Project (PCaP), a cohort of 2,106 incident CaP cases (2063 with complete ethnicity information) comprising roughly equal numbers of research subjects reporting as Black/African American (AA) or European American/Caucasian/Caucasian American/White (EA) from North Carolina or Louisiana. Mean genome wide individual ancestry estimates of percent African, European and Asian were obtained and tested for differences by state and ethnicity (Cajun and/or Creole and Hispanic/Latino) using multivariate analysis of variance models. Principal components (PC) were compared to assess differences in genetic composition by self-reported race and ethnicity between and within states.ResultsMean individual ancestries differed by state for self-reporting AA (p = 0.03) and EA (p = 0.001). This geographic difference attenuated for AAs who answered "no" to all ethnicity membership questions (non-ethnic research subjects; p = 0.78) but not EA research subjects, p = 0.002. Mean ancestry estimates of self-identified AA Louisiana research subjects for each ethnic group; Cajun only, Creole only and both Cajun and Creole differed significantly from self-identified non-ethnic AA Louisiana research subjects. These ethnicity differences were not seen in those who self-identified as EA.ConclusionsMean IA differed by race between states, elucidating a potential contributing factor to these differences in AA research participants: self-reported ethnicity. Accurately accounting for genetic admixture in this cohort is essential for future analyses of the genetic and environmental contributions to CaP.

Dataset Information

Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects.

Publications

Assessing differences in inhaled corticosteroid response by self-reported race-ethnicity and genetic ancestry among asthmatic subjects.

Similar Datasets

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