Gene-based association identifies SPATA13-AS1 as a pharmacogenomic predictor of inhaled short-acting beta-agonist response in multiple population groups

B Padhukasahasram; J J Yang; A M Levin; M Yang; E G Burchard; R Kumar; P-Y Kwok; M A Seibold; D E Lanfear; L K Williams

doi:10.1038/tpj.2013.49

Gene-based association identifies SPATA13-AS1 as a pharmacogenomic predictor of inhaled short-acting beta-agonist response in multiple population groups

Pharmacogenomics J. 2014 Aug;14(4):365-71. doi: 10.1038/tpj.2013.49. Epub 2014 Jan 14.

Authors

B Padhukasahasram¹, J J Yang², A M Levin², M Yang¹, E G Burchard³, R Kumar⁴, P-Y Kwok⁵, M A Seibold⁶, D E Lanfear⁷, L K Williams⁷

Affiliations

¹ Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA.
² Department of Public Health Sciences, Henry Ford Health System, Detroit, MI, USA.
³ 1] Department of Medicine, University of California San Francisco, San Francisco, CA, USA [2] Department of Bioengineering and Therapeutic Sciences, University of California San Francisco, San Francisco, CA, USA.
⁴ Department of Pediatrics, The Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
⁵ 1] Department of Dermatology, University of California San Francisco, San Francisco, CA, USA [2] Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA.
⁶ 1] Integrated Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, Colorado, USA [2] Department of Pediatrics, National Jewish Health, Denver, CO, USA [3] Division of Pulmonary Sciences and Critical Care Medicine, Department of Medicine, University of Colorado Denver, Denver, CO, USA.
⁷ 1] Center for Health Policy and Health Services Research, Henry Ford Health System, Detroit, MI, USA [2] Department of Medicine, Henry Ford Health System, Detroit, MI, USA.

Abstract

Inhaled short-acting beta-agonist (SABA) medication is commonly used in asthma patients to rapidly reverse airway obstruction and improve acute symptoms. We performed a genome-wide association study of SABA medication response using gene-based association tests. A linear mixed model approach was first used for single-nucleotide polymorphism associations, and the results were later combined using GATES to generate gene-based associations. Our results identified SPATA13-AS1 as being significantly associated with SABA bronchodilator response in 328 healthy African Americans. In replication, this gene was associated with SABA response among the two separate groups of African Americans with asthma (n=1073, P=0.011 and n=1968, P=0.014), 149 healthy African Americans (P=0.003) and 556 European Americans with asthma (P=0.041). SPATA13-AS1 was also associated with longitudinal SABA medication usage in the two separate groups of African Americans with asthma (n=658, P=0.047 and n=1968, P=0.025). Future studies are needed to delineate the precise mechanism by which SPATA13-AS1 may influence SABA response.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Administration, Inhalation
Adrenergic beta-Agonists / administration & dosage*
Adult
Asthma / drug therapy*
Asthma / genetics
Black or African American
Female
Genome-Wide Association Study*
Guanine Nucleotide Exchange Factors / genetics*
Humans
Male
Middle Aged
Pharmacogenetics*
Polymorphism, Single Nucleotide*
Population Groups

Substances

Adrenergic beta-Agonists
Guanine Nucleotide Exchange Factors
SPATA13 protein, human

Abstract

Publication types

MeSH terms

Substances

Grants and funding