GR gene polymorphism is associated with inter-subject variability in response to glucocorticoids in patients with myasthenia gravis

• Published in: European journal of neurology Vol. 23; no. 8; pp. 1372 - 1379
• Main Authors: Xie, Y., Meng, Y., Li, H.-F., Hong, Y., Sun, L., Zhu, X., Yue, Y.-X., Gao, X., Wang, S., Li, Y., Kusner, L. L., Kaminski, H. J.
• Format: Journal Article
• Language: English
• Published: England Blackwell Publishing Ltd 01.08.2016; John Wiley & Sons, Inc
• Subjects: Adult; Alleles; Cohort Studies; Female; Genes; glucocorticoid receptor; Glucocorticoids - therapeutic use; Humans; Male; Middle Aged; myasthenia gravis; Myasthenia Gravis - drug therapy; Myasthenia Gravis - genetics; Pharmacogenetics; Polymorphism, Single Nucleotide; Receptors, Glucocorticoid - genetics; single nucleotide polymorphism; treatment efficacy; variability; myasthenia gravis; glucocorticoid receptor; variability; single nucleotide polymorphism; treatment efficacy
• ISSN: 1351-5101; 1468-1331; 1468-1331
• DOI: 10.1111/ene.13040

Background and purpose Glucocorticoids (GCs) are the mainstay treatment of myasthenia gravis (MG). However, wide inter‐individual variability exists in the response to GCs. Methods A Chinese cohort of 257 MG patients treated with GCs was evaluated for the association between 19 single nucleotide polymorphisms in the GR gene and clinical response to the initial 3 month GC therapy. A quantitative MG score decreasing by ≥3 units or becoming zero was defined as sensitivity to GCs. Results The rs17209237* G allele was less frequent in the GC insensitive group compared with the GC sensitive group [P = 0.013, odds ratio (OR) 0.119]. The rs9324921* A allele was more frequent in the GC insensitive group than in the GC sensitive group (P = 0.046, OR 1.94). Carriers of the rs17209237 G allele were less frequent in the GC insensitive group than in the GC sensitive group (dominant model, P = 0.009). Carriers of the rs9324921 A allele were more frequent in the GC insensitive group than in the GC sensitive group (dominant model, P = 0.037). Multivariate logistic regression revealed that the rs17209237 G allele carrier (P = 0.037, OR 0.12) and disease duration before GC treatment (P = 0.011, OR 3.45) were independent factors that contributed to GC efficacy. Conclusion rs17209237 in the GR gene was identified as an independent factor that contributes to GC efficacy in MG patients. The genetic variations of the GR gene may play a role in predicting response to GC treatment.