| Autor: |
Loren C. Denlinger, Jerry A. Krishnan, Maria Pino-Yanes, Hengameh Raissy, Wayne J. Morgan, Manuela Cernadas, Michael D. Cabana, Daniel J. Jackson, J. Tod Olin, David Kantor, Julian Solway, Nicole Grossman, Elizabeth J. Ampleford, Jonathan M. Gaffin, Ronina Covar, Corey Cox, Michael E. Wechsler, James F. Chmiel, Elliot Israel, Kathleen C. Barnes, Steven R. White, Lisa Sullivan-Vedder, Stephen C. Lazarus, Fernando Holguin, Gregory A. Hawkins, Anne M. Fitzpatrick, Jason E. Lang, Vernon M. Chinchilli, Harsha Kumar, Jacqueline A. Pongracic, Max A. Seibold, Njira L Lugogo, Esteban G. Burchard, Angel C.Y. Mak, Fernando D. Martinez, Esther Herrera-Luis, Stephen P. Peters, James N. Moy, Lewis J. Smith, Victor E. Ortega, Sachin Baxi, Craig F. LaForce, Perdita Permaul, Marissa Hautpman, John J. Lima, Wanda Phipatanakul, Tarig Ali-Dinar, Michelle Daya, Juan Carlos Cardet, Kristie Ross, Nizar N. Jarjour, Christine A. Sorkness, Celeste Eng, Robert F. Lemanske, Susan J. Kunselman, Monica Kraft, Rachel G. Robison, Stanley J. Szefler, Deborah A. Meyers, Deborah Gentile, Mario Castro, Satria P Sajuthi, Dayna Long, Dave Mauger, Margee Louisias, Elizabeth Burke-Roberts, Donglei Hu, Ross E. Myers, Sally E. Wenzel, Kathryn V. Blake, Avraham Beigelman, Lakeia Wright, Mindy Benson, Leonard B. Bacharier, Eugene R. Bleecker, Wendy C. Moore, Emily DiMango, Loretta Que, Edward T. Naureckas, Lisa Bartnikas, William Sheehan |
| Rok vydání: |
2021 |
| Předmět: |
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| Zdroj: |
The Lancet. Child & adolescent health, vol 5, iss 12
Lancet Child Adolesc Health |
| Popis: |
BACKGROUND Pharmacogenetic studies in asthma cohorts, primarily made up of White people of European descent, have identified loci associated with response to inhaled beta agonists and corticosteroids (ICSs). Differences exist in how individuals from different ancestral backgrounds respond to long-acting beta agonist (LABA) and ICSs. Therefore, we sought to understand the pharmacogenetic mechanisms regulating therapeutic responsiveness in individuals of African descent. METHODS We did ancestry-based pharmacogenetic studies of children (aged 5-11 years) and adolescents and adults (aged 12-69 years) from the Best African Response to Drug (BARD) trials, in which participants with asthma uncontrolled with low-dose ICS (fluticasone propionate 50 μg in children, 100 μg in adolescents and adults) received different step-up combination therapies. The hierarchal composite outcome of pairwise superior responsiveness in BARD was based on asthma exacerbations, a 31-day difference in annualised asthma-control days, or a 5% difference in percentage predicted FEV1. We did whole-genome admixture mapping of 15 159 ancestral segments within 312 independent regions, stratified by the two age groups. The two co-primary outcome comparisons were the step up from low-dose ICS to the quintuple dose of ICS (5 × ICS: 250 μg twice daily in children and 500 μg twice daily in adolescents and adults) versus double dose (2-2·5 × ICS: 100 μg twice daily in children, 250 μg twice daily in adolescents and adults), and 5 × ICS versus 100 μg fluticasone plus a LABA (salmeterol 50 μg twice daily). We used a genome-wide significance threshold of p |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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