Format

Send to

Choose Destination
J Neurol Sci. 2016 Apr 15;363:165-9. doi: 10.1016/j.jns.2016.02.054. Epub 2016 Feb 23.

Sequencing analysis of the human glucocorticoid receptor (NR3C1) gene in multiple sclerosis patients.

Author information

1
Department of Biological Chemistry, National and Kapodistrian University of Athens, Medical School, Mikras Asias 75, 11527 Athens, Greece.
2
Division of Endocrinology, Metabolism and Diabetes, First Department of Pediatrics, 'Aghia Sophia' Children's Hospital, National and Kapodistrian University of Athens, Medical School, Athens, Greece.
3
1st Department of Psychiatry, University Hospital 'Eginition', Medical School, National and Kapodistrian University of Athens, Vassilissis Sophias 74, 11528 Athens, Greece.
4
Department of Animal Breeding, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece.
5
Department of Biological Chemistry, National and Kapodistrian University of Athens, Medical School, Mikras Asias 75, 11527 Athens, Greece; Department of Clinical Biochemistry, University Hospital "ATTIKO", Medical School, National and Kapodistrian University of Athens, 1 Rimini, Haidari, 12462 Athens, Greece. Electronic address: pmoutsatsou@med.uoa.gr.

Abstract

Various specific human glucocorticoid receptor (NR3C1) gene polymorphisms have been described in multiple sclerosis (MS) patients and correlated with disease progression, susceptibility and aggressiveness. Herein, we investigated the presence of gene alterations in the entire coding region of the NR3C1 in MS patients of variable clinical status (CIS, RRMS and SPMS) and the association(s) of these alterations with severity of disease (EDSS), response to glucocorticoid (GC) treatment and clinical improvement. Sixty Caucasian Greek MS patients were included. Sequencing the coding sequences and intron-exon boundaries of the NR3C1 did not reveal the presence of mutation(s) in any of the MS patients. Three previously described polymorphisms were detected: p.N363S (rs6195), p.N766N (rs6196) and c.1469-16G>T (rs6188). None of the identified alleles/genotypes were found to be associated with the severity of disease, response to glucocorticoids and disease subtypes. Known polymorphism, such as ER22/23EK that has been previously detected in MS patients, was not detected. There is a considerable ethnicity-related variation in the frequency of the NR3C1 polymorphisms. Although a genetic basis of the glucocorticoid sensitivity exists in healthy population, in the presence of chronic inflammation and abundance of cytokines--such in MS patients--other factors appear to play a more important role in GC sensitivity.

KEYWORDS:

Disease activity; Glucocorticoid receptor; Multiple sclerosis; Mutation; Polymorphism

PMID:
27000245
DOI:
10.1016/j.jns.2016.02.054
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center