rs37973

rs37973 is a SNP in the promoter region of the glucocorticoid induced transcript 1 GLCCI1 gene on chromosome 7. In asthmatics corticosteroid treatment increases GLCCI1 protein in lung white blood cells. This increase is suggested to be followed by the inflammatory cells apoptosis and resolution of the inflammation. The amount of GLCCI1 protein induced by glucocorticoids was significantly lower in the bronchial epithelial cells of rs37973(G;G) patients as compared to wild type homozygotes possibly resulting in inferior response.. Based on 4 populations totaling 900+ asthma patients, the rs37973(G) allele was associated (p = 0.0007, pooled data) with less improvement of lung function in response to inhaled glucocorticoids such as budesonide. The mean (±SE) increase in forced expiratory volume in 1 second (FEV1) in treated rs37973(G;G) patients was about one third of that seen in rs37973(A;A) patients (3.2±1.6% vs. 9.4±1.1%). Based on dividing the response into highest vs lowest quartiles of response, the allelic odds ratio of falling into the lowest responding quartile based on an additive genetic model was calculated to be 1.52 (CI: 1.13 - 2.03). Genotype accounted for about 7% of overall inhaled glucocorticoid response variability. This result failed to replicate in an analysis of corticosteroid clinical trials in a population of 1,900 non-Hispanic white patients with asthma. rs37973 did not influence change from baseline in forced expiratory volume. There was only a non-significant trend toward less response in rs37973(G;G) patients. In a study of 400 Japanese patients with bronchial asthma receiving inhaled corticosteroids, the pulmonary function was not significantly different in rs37973(G;G) compared with rs37973(A;A) genotypes. However, rs37973(G;G) was associated with about 3-fold increased odds of requiring further treatment in addition to inhaled corticosteroids, principally, tiotropium and anti-IgE (omalizumab)..