Y Xie1,2, Y Meng3, H-F Li4, Y Hong5, L Sun6, X Zhu6, Y-X Yue4, X Gao5, S Wang1, Y Li1, L L Kusner7, H J Kaminski2. 1. Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing, China. 2. Department of Neurology, George Washington University, Washington, DC, USA. 3. Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing, China. 4. Department of Neurology, Qilu Hospital of Shandong University, Jinan, China. 5. Department of Neurology, Affiliated Hospital of Qingdao University, Qingdao, China. 6. Key Laboratory of Geriatrics, Beijing Hospital and Beijing Institute of Geriatrics, Ministry of Health, Beijing, China. 7. Departments of Pharmacology and Physiology, George Washington University, Washington, DC, USA.
Abstract
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.
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 MGpatients 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 MGpatients. The genetic variations of the GR gene may play a role in predicting response to GC treatment.