Premium
Association of corticotropin releasing factor receptor‐2 variants with response to inhaled glucocorticoids in asthma
Author(s) -
Silverman E. S.,
Lake S. L.,
Tantisira K. G.,
Richter B. G.,
Litonjua A. A.,
Lazarus R.,
Valone J.,
Shore S. A.,
Weiss S. T.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.11.032
Subject(s) - glucocorticoid receptor , single nucleotide polymorphism , glucocorticoid , confounding , medicine , endocrinology , asthma , haplotype , pharmacogenomics , allele , genetic association , gene , biology , genotype , pharmacology , genetics
Background Corticotropin releasing factor receptor‐2 (CRFR2) is a G‐protein‐coupled receptor that regulates the levels of glucocorticoids and the tone of smooth muscle. Because genetic variants in the homologous receptor CRFR1 have been associated with altered glucocorticoid response in asthmatics, we hypothesized that there exist variants in CRFR2 that are associated with altered therapeutic response. Methods We genotyped 16 SNPs in CRFR2 in two clinical trial populations: 311 childhood asthmatics treated with glucocorticoids for 8 weeks and 336 adult asthmatics treated with glucocorticoids for 8 weeks. The association of single SNPs and haplotypes with glucocorticoid response at 8 weeks was explored with response measured as a change in the FEV1 as a continuous trait. FEV1 was adjusted for age, height, and sex as covariates. Only Caucasians were included in the analysis to minimize the confounding effects of population stratification. Results Two CRFR2 SNPs (rs973002 and rs1003929) were associated (p< 0.05) with glucocorticoid response in the childhood asthma study and one of these SNPs (rs973002, minor allele frequency 0.17) was also associated with glucocorticoid response in the adult study. Conclusion CRFR2 gene variants may be associated with therapeutic response to glucocorticoids in asthmatics. These findings suggest that the genes of the CRF pathway may be an important genetic source of therapeutic heterogeneity. Clinical Pharmacology & Therapeutics (2005) 77 , P8–P8; doi: 10.1016/j.clpt.2004.11.032