Polymorphisms in the Glucocorticoid Receptor Gene and Associations with Glucocorticoid-Induced Avascular Osteonecrosis of the Femoral Head.

Abstract

Individual sensitivity to glucocorticoid (GC) therapy might play a pivotal role in the development of GC-induced avascular necrosis of the femoral head (GANFH). In a growing number of studies, common polymorphisms of the glucocorticoid receptor gene (nuclear receptor subfamily 3 group C member 1 [NR3C1]) have been associated with variability in the individual sensitivity to GCs. However, whether the NR3C1 gene polymorphisms actually influence the susceptibility of GANFH remains unknown. In this study, we report the findings of a case-control study to investigate the role of the NR3C1 gene single-nucleotide polymorphisms (SNPs) in GANFH susceptibility among 78 GANFH patients (GCs sensitive) and 115 GC-resistant controls. Our results found no significant associations between the SNPs N363S, Tth111I, BclI, ER22/23EK, and A3669G with GANFH susceptibility. The G allele frequency, both homozygous and heterozygous, of SNP BclI was significantly different between control and GANFH combined with osteopenia subgroups (odds ratios [OR] = 1.81; 95% confidence intervals [CI] = 1.05-3.10; OR = 2.04; 95% CI = 1.03-4.07, respectively). Most of these common SNPs in the NR3C1 gene likely do not play critical roles in the susceptibility of GANFH. However, the G allele at the SNP Bcll, irrespective of dosage, may increase risk for the development of GANFH combined with osteopenia in the Chinese population.