Genetic variants of GSNOR and ADRB2 influence response to albuterol in African-American children with severe asthma.
African Americans are disproportionately affected by asthma. Social and economic factors play a role in this disparity, but there is evidence that genetic factors may also influence the development of asthma and response to therapy in African American children. Our hypothesis is that variations in asthma related genes contribute to the observed asthma disparities by influencing the response to asthma-specific therapy. In order to test this hypothesis, we characterized the clinical response to asthma-specific therapy in 107 African American children who presented to the emergency room in status asthmaticus, with a primary outcome indicator of length of time on continuous albuterol. Single locus analysis indicated that genotype variation in glutathione-dependent S-nitrosoglutathione reductase (GSNOR) is associated with a decreased response to asthma treatment in African American children. A post hoc multi-locus analysis revealed that a combination of four single nucleotide polymorphisms (SNPs) within GSNOR, adrenergic receptor beta 2, and carbamoyl phosphate synthetase-1 give a 70% predictive value for lack of response to therapy. This predictive model needs replication in other cohorts of patients with asthma, but suggests gene-gene interactions may have greater significance than that identified with single variants. Our findings also suggest that genetic variants may contribute to the observed population disparities in asthma.
Moore
Paul E
PE
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-9500, USA.
Ryckman
Kelli K
KK
Williams
Scott M
SM
Patel
Neal
N
Summar
Marshall L
ML
Sheller
James R
JR
D000293:Adolescent; D001741:Black or African American / Q000235:genetics*; D000420:Albuterol / Q000627:therapeutic use*; D000445:Aldehyde Oxidoreductases / Q000235:genetics*; D001249:Asthma / Q000188:drug therapy / Q000235:genetics*; D001993:Bronchodilator Agents / Q000627:therapeutic use*; D002648:Child; D002675:Child, Preschool; D004351:Drug Resistance / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D010597:Pharmacogenetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics
D001993:Bronchodilator Agents; D018343:Receptors, Adrenergic, beta-2; D000445:Aldehyde Oxidoreductases; C087006:formaldehyde dehydrogenase, glutathione-independent; D000420:Albuterol