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.