Asthma steroid pharmacogenetics: a study strategy to identify replicated treatment responses.
Asthma treatment with inhaled steroids demonstrates significant between-person variability. Genetic variation could contribute to this response to inhaled glucocorticosteroids. Difficulties in performing genetic association studies are well known. We designed a test and validation strategy to assess steroid pathway candidate genes. One hundred thirty-one single nucleotide polymorphisms in 14 candidate genes in the steroid pathway were genotyped in an 8-week clinical trial of 470 adults with moderate to severe asthma. We then validated our findings in a second population of individuals with childhood asthma in a 4-year clinical trial of inhaled corticosteroids and a third population of adults with asthma. One gene, corticotrophin-releasing hormone receptor 1 (CRHR1, NM_004382), demonstrated multiple single nucleotide polymorphism associations within each of the three populations. The approach of a test and multiple replication populations is a valuable strategy in asthma pharmacogenetics, which can insure valid association findings.
Published In/Presented At
Weiss, S. T., Lake, S. L., Silverman, E. S., Silverman, E. K., Richter, B., Drazen, J. M., & Tantisira, K. G. (2004). Asthma steroid pharmacogenetics: a study strategy to identify replicated treatment responses. Proceedings of the American Thoracic Society, 1(4), 364–367. https://doi.org/10.1513/pats.200409-043MS
Medicine and Health Sciences
Department of Medicine