Identification of polymorphisms in the human glucocorticoid receptor gene (NR3C1) in a multi-racial asthma case and...

The glucocorticoid receptor (GR) gene (NR3C1) maps to 5q31, a region genetically linked to asthma. In this study, NR3C1 exons 1A, 1B, and exons 1C to 9 (alpha and beta) were sequenced in a screening panel of asthmatics and unaffected controls from US Caucasian, African American, US Hispanic, and Dutch Caucasian populations to identify polymorphisms for genetic association studies. Eight polymorphisms were identified in exon 1A, but none were located in putative transcription regulatory sites. Thirty-four polymorphisms were identified in exons 1B to 9 (alpha and beta), 17 of which were novel. Eight coding polymorphisms were identified (4 non-synonymous). One novel mutation (Ala229Thr) was identified in a Hispanic individual. Linkage disequilibrium (LD) was strongest between polymorphisms spanning intron 2 to exon 9beta. This data shows the variability of NR3C1 polymorphism frequencies between racial groups and confirms that NR3C1 non-synonymous coding polymorphisms are generally rare in mild/moderate asthmatics and unaffected controls.