title: Sequencing analysis of the human glucocorticoid receptor (NR3C1) gene in multiple sclerosis patients.
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.
authors.affiliation: Department of Biological Chemistry, National and Kapodistrian University of Athens, Medical School, Mikras Asias 75, 11527 Athens, Greece.
authors.forename: Eva
authors.initials: E
authors.lastname: Kassi
authors.affiliation: Department of Biological Chemistry, National and Kapodistrian University of Athens, Medical School, Mikras Asias 75, 11527 Athens, Greece.
authors.forename: Anna
authors.initials: A
authors.lastname: Semaniakou
authors.affiliation: 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.
authors.forename: Amalia
authors.initials: A
authors.lastname: Sertedaki
authors.affiliation: 1st Department of Psychiatry, University Hospital 'Eginition', Medical School, National and Kapodistrian University of Athens, Vassilissis Sophias 74, 11528 Athens, Greece.
authors.forename: Maria-Eleftheria
authors.initials: ME
authors.lastname: Evangelopoulos
authors.affiliation: Department of Biological Chemistry, National and Kapodistrian University of Athens, Medical School, Mikras Asias 75, 11527 Athens, Greece.
authors.forename: Theodosia
authors.initials: T
authors.lastname: Kazazoglou
authors.affiliation: Department of Animal Breeding, Agricultural University of Athens, Iera Odos 75, 11855 Athens, Greece.
authors.forename: Antonios
authors.initials: A
authors.lastname: Kominakis
authors.affiliation: 1st Department of Psychiatry, University Hospital 'Eginition', Medical School, National and Kapodistrian University of Athens, Vassilissis Sophias 74, 11528 Athens, Greece.
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sfagos
authors.affiliation: 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.
authors.forename: Evangelia
authors.initials: E
authors.lastname: Charmandari
authors.affiliation: 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.
authors.forename: George P
authors.initials: GP
authors.lastname: Chrousos
authors.affiliation: 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.
authors.forename: Paraskevi
authors.initials: P
authors.lastname: Moutsatsou
mesh_terms: D000328:Adult; D005260:Female; D006115:Greece / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011965:Receptors, Glucocorticoid / Q000235:genetics*; D017422:Sequence Analysis, DNA / Q000379:methods; D044465:White People / Q000235:genetics
chemical_list: C497713:NR3C1 protein, human; D011965:Receptors, Glucocorticoid
keywords: Disease activity; Glucocorticoid receptor; Multiple sclerosis; Mutation; Polymorphism