Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Neurological Sciences
Published in: Neurological Sciences 10/2020

Open Access 01-10-2020 | Multiple Sclerosis | Original Article

Glucocorticoid receptor mutations and clinical sensitivity to glucocorticoid in Chinese multiple sclerosis patients

Authors: Tian Song, Haoxiao Chang, Li Du, Linlin Yin, Fudong Shi, Xinghu Zhang

Published in: Neurological Sciences | Issue 10/2020

Login to get access

Abstract

Background

Glucocorticoid (GC) is the first-line therapy in acute attacks of multiple sclerosis (MS), but its efficacy is individually variable and may be associated with glucocorticoid receptor (GR) gene.

Objective

To establish the association between GR gene sequence and clinical GC sensitivity in Chinese MS patients. And to investigate the expression differences of serum GRα and FK506 binding protein 5 (FKBP5) in GC responders and non-responders.

Materials and methods

Coding exons 2–9 of the GR gene from 97 MS patients were sequenced. We performed ELISA to detect serum GRα and FKBP5 before the GC impulse therapy in patients with different GC sensitivities (according to the EDSS changes before and after the GC medication).

Results

Seven new mutations were located in exon 2, but the presence or absence of mutations was not associated with the response to GC therapy (P = 0.416). The GC-sensitive patients had higher GRα (P = 0.011) but lower FKBP5 (P = 0.025) levels in the serum.

Conclusions

The GR mutations detected in our study were not associated with the response to GC in Chinese MS patients. Higher GRα and lower FKBP5 levels in the serum might predict the response to GC, which may provide potential therapeutic target for GC-resistant patients with acute MS attack.
Appendix
Available only for authorised users
Literature
1.
Goodin DS (2014) Glucocorticoid treatment of multiple sclerosis. Handb Clin Neurol 122:455–464CrossRef
2.
Gold SM, Sasidhar MV, Lagishetty V, Spence RD, Umeda E, Ziehn MO, Krieger T, Schulz KH, Heesen C, Hewison M, Voskuhl RR (2012) Dynamic development of glucocorticoid resistance during autoimmune neuroinflammation. J Clin Endocrinol Metab 97(8):E1402–E1410CrossRef
3.
Trojano M, Bergamaschi R, Amato MP, Comi G, Ghezzi A, Lepore V, Marrosu MG, Mosconi P, Patti F, Ponzio M, Zaratin P, Battaglia MA, Italian Multiple Sclerosis Register Centers Group (2019) The Italian multiple sclerosis register. Neurol Sci 40(1):155–165CrossRef
4.
Cain DW, Cidlowski JA (2017) Immune regulation by glucocorticoids. Nat Rev Immunol 17(4):233–247CrossRef
5.
Ramamoorthy S, Cidlowski JA (2013) Exploring the molecular mechanisms of glucocorticoid receptor action from sensitivity to resistance. Endocr Dev 24:41–56CrossRef
6.
Quax RA, Manenschijn L, Koper JW, Hazes JM, Lamberts SW, van Rossum E, Feelders RA (2013) Glucocorticoid sensitivity in health and disease. Nat Rev Endocrinol 9(11):670–686CrossRef
7.
Fries GR, Gassen NC, Rein T (2017) The FKBP51 glucocorticoid receptor co-chaperone: regulation, function, and implications in health and disease. Int J Mol Sci 18(12)
8.
Caratti G, Matthews L, Poolman T, Kershaw S, Baxter M, Ray D (2015) Glucocorticoid receptor function in health and disease. Clin Endocrinol 83(4):441–448CrossRef
9.
Koper JW, van Rossum EF, van den Akker EL (2014) Glucocorticoid receptor polymorphisms and haplotypes and their expression in health and disease. Steroids. 92:62–73CrossRef
10.
van Winsen LL, Hooper-van Veen T, van Rossum EF, Polman CH, van den Berg T, Koper JW, Uitdehaag BM (2005) The impact of glucocorticoid receptor gene polymorphisms on glucocorticoid sensitivity is outweighted in patients with multiple sclerosis. J Neuroimmunol 167(1–2):150–156CrossRef
11.
van Winsen LM, Manenschijn L, van Rossum EF, Crusius JB, Koper JW, Polman CH, Uitdehaag BM (2009) A glucocorticoid receptor gene haplotype (TthIII1/ER22/23EK/9beta) is associated with a more aggressive disease course in multiple sclerosis. J Clin Endocrinol Metab 94(6):2110–2114CrossRef
12.
Thompson AJ, Banwell BL, Barkhof F, Carroll WM, Coetzee T, Comi G, Correale J, Fazekas F, Filippi M, Freedman MS, Fujihara K, Galetta SL, Hartung HP, Kappos L, Lublin FD, Marrie RA, Miller AE, Miller DH, Montalban X, Mowry EM, Sorensen PS, Tintoré M, Traboulsee AL, Trojano M, Uitdehaag BMJ, Vukusic S, Waubant E, Weinshenker BG, Reingold SC, Cohen JA (2018) Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol 17(2):162–173CrossRef
13.
Kassi E, Semaniakou A, Sertedaki A, Evangelopoulos ME, Kazazoglou T, Kominakis A, Sfagos C, Charmandari E, Chrousos GP, Moutsatsou P (2016) Sequencing analysis of the human glucocorticoid receptor (NR3C1) gene in multiple sclerosis patients. J Neurol Sci 363:165–169CrossRef
14.
van Oosten MJ, Dolhain RJ, Koper JW, van Rossum E, Emonts M, Han KH, Wouters JM, Hazes JM, Lamberts SW, Feelders RA (2010) Polymorphisms in the glucocorticoid receptor gene that modulate glucocorticoid sensitivity are associated with rheumatoid arthritis. Arthritis Res Ther 12(4):R159CrossRef
15.
Melief J, Koper JW, Endert E, Møller HJ, Hamann J, Uitdehaag BM, Huitinga I (2016) Glucocorticoid receptor haplotypes conferring increased sensitivity (BclI and N363S) are associated with faster progression of multiple sclerosis. J Neuroimmunol 299:84–89CrossRef
16.
Manenschijn L, van den Akker EL, Lamberts SW, van Rossum EF (2009) Clinical features associated with glucocorticoid receptor polymorphisms. An overview. Ann N Y Acad Sci 1179:179–198CrossRef
17.
Santen RJ, Jewell CM, Yue W, Heitjan DF, Raff H, Katen KS, Cidlowski JA (2018) Glucocorticoid receptor mutations and hypersensitivity to endogenous and exogenous glucocorticoids. J Clin Endocrinol Metab 103(10):3630–3639CrossRef
18.
van Winsen LM, Hooper-van Veen T, van Rossum EF, Koper JW, Barkhof F, Polman CH, Uitdehaag BM (2007) Glucocorticoid receptor gene polymorphisms associated with more aggressive disease phenotype in MS. J Neuroimmunol 186(1–2):150–155CrossRef
19.
Dekker MJ, van den Akker EL, Koper JW, Manenschijn L, Geleijns K, Ruts L, van Rijs W, Tio-Gillen AP, van Doorn P, Lamberts SW, Jacobs BC (2009) Effect of glucocorticoid receptor gene polymorphisms in Guillain-Barré syndrome. J Peripher Nerv Syst 14(2):75–83CrossRef
20.
Souza MC, Martins CS, Silva-Junior IM, Chriguer RS, Bueno AC, Antonini SR, Silva WA Jr, Zago MA, Moreira AC, Castro Md (2014) NR3C1 polymorphisms in Brazilians of Caucasian, African, and Asian ancestry: glucocorticoid sensitivity and genotype association. Arq Bras Endocrinol Metabol 58(1):53–61CrossRef
21.
Chun E, Lee HS, Bang BR, Kim TW, Lee SH, Kim JH, Cho SH, Min KU, Kim YY, Park HW (2011) Dexamethasone-induced FKBP51 expression in peripheral blood mononuclear cells could play a role in predicting the response of asthmatics to treatment with corticosteroids. J Clin Immunol 31(1):122–127CrossRef
22.
Tajiri T, Matsumoto H, Niimi A, Ito I, Oguma T, Nakaji H, Inoue H, Iwata T, Nagasaki T, Kanemitsu Y, Petrova G, Mishima M (2013) Association of eosinophilic inflammation with FKBP51 expression in sputum cells in asthma. PLoS One 8(6):e65284CrossRef
23.
Ratajczak T, Cluning C, Ward BK (2015) Steroid receptor-associated immunophilins: a gateway to steroid signalling. Clin Biochem Rev 36(2):31–52PubMedPubMedCentral
24.
Maiarù M, Morgan OB, Mao T, Breitsamer M, Bamber H, Pöhlmann M, Schmidt MV, Winter G, Hausch F, Géranton SM (2018) The stress regulator FKBP51: a novel and promising druggable target for the treatment of persistent pain states across sexes. Pain. 159(7):1224–1234CrossRef
25.
Kästle M, Kistler B, Lamla T, Bretschneider T, Lamb D, Nicklin P, Wyatt D (2018) FKBP51 modulates steroid sensitivity and NFκB signalling: a novel anti-inflammatory drug target. Eur J Immunol 48(11):1904–1914CrossRef
26.
Baldin E, Riise T, Mattarozzi K, Gajofatto A, Granella F, Leone M, Lugaresi A, Malagù S, Motti L, Neri W, Pesci I, Santangelo M, Scandellari C, Tola MR, Vignatelli L, Zenesini C, D’Alessandro R, G.E.Ro.N.I.Mu.S. study group (2019) Health-related quality of life in clinically isolated syndrome and risk of conversion to multiple sclerosis. Neurol Sci 40(1):75–80CrossRef
27.
Tacchino A, Brichetto G, Zaratin P, Battaglia MA, Ponzio M (2019) Self-assessment reliability in multiple sclerosis: the role of socio-demographic, clinical, and quality of life aspects. Neurol Sci 40(3):617–620CrossRef
Metadata
Title
Glucocorticoid receptor mutations and clinical sensitivity to glucocorticoid in Chinese multiple sclerosis patients
Authors
Tian Song
Haoxiao Chang
Li Du
Linlin Yin
Fudong Shi
Xinghu Zhang
Publication date
01-10-2020
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 10/2020
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-020-04376-8

Other articles of this Issue 10/2020

Neurological Sciences 10/2020 Go to the issue

Letter to the Editor

An unusual case of anti-basal ganglia encephalitis showing polyradiculoneuritis features

Review Article

Improving care of chronic pain patients with spinal cord stimulator therapy amidst the opioid epidemic

Original Article

Differences in correlations of depression and anhedonia with cardiovascular sympathetic functions during a head-up tilt test in drug-naïve Parkinson’s disease patients

Original Article

MyomiRNAs and myostatin as physical rehabilitation biomarkers for myotonic dystrophy

Brief Communication

Appropriateness, safety, and effectiveness of “drip and ship” teleconsultation model in Southeastern Tuscany: a feasibility study

Letter to the Editor

Advance care planning and mental capacity in ALS: a current challenge for an unsolved matter