title: Glucocorticoid receptor variants may predispose to rheumatoid arthritis susceptibility.
abstract: OBJECTIVE
  Deregulation of glucocorticoid (GC) secretion could be associated with rheumatoid arthritis (RA). The GC receptor (GR) has two isoforms. In the present study, we explored the role of GR-alpha polymorphisms rs33388, rs33389, and Bcl I, and the GR-beta variant rs6198 in RA susceptibility.
  
  
  METHODS
  One hundred and thirty-six RA patients and 148 ethnic matching controls were studied. Polymorphisms rs33388 and Bcl I were genotyped by polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP), and variants rs33389 and rs6198 by polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) coupled with sequencing. Arlequin and SPSS softwares were used in the statistical analysis.
  
  
  RESULTS
  The polymorphisms studied were in Hardy-Weinberg equilibrium in both groups. A marginally statistical significant difference was observed in the distribution of rs33388 genotypes between RA patients and controls (p = 0.053). When the A and T alleles were compared, the statistical significance was p = 0.025. Specific complex genotypes were also differentially distributed: the GR-alpha complex genotypes (a) [homozygote (homo) wild-type (wt) rs33388-homo wt rs33389] (11% RA vs. 21% controls; p = 0.023), (b) [homo wt rs33388-homo wt rs33389-homo non-wt Bcl I] (0.7% RA vs. 4.7% controls; p = 0.042), and (c) the GR-beta complex genotype [homo wt rs33388-homo wt rs33389-homo non-wt Bcl I-homo wt rs6198] (0.7% RA vs. 4.7% controls; p = 0.042).
  
  
  CONCLUSIONS
  GR-alpha and GR-beta polymorphisms are potentially associated with RA susceptibility. However, additional studies in larger and other ethnic groups of patients are needed to confirm the results of the present study.
authors.affiliation: Genetics Unit, Department of Obstetrics and Gynaecology, Medical School, University of Ioannina, Ioannina, Greece.
authors.forename: A
authors.initials: A
authors.lastname: Chatzikyriakidou
authors.forename: I
authors.initials: I
authors.lastname: Georgiou
authors.forename: P V
authors.initials: PV
authors.lastname: Voulgari
authors.forename: A N
authors.initials: AN
authors.lastname: Georgiadis
authors.forename: E S
authors.initials: ES
authors.lastname: Argyriou
authors.forename: A A
authors.initials: AA
authors.lastname: Drosos
mesh_terms: D000368:Aged; D001172:Arthritis, Rheumatoid / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000235:genetics*
chemical_list: D011965:Receptors, Glucocorticoid; C411470:glucocorticoid receptor alpha; C121943:glucocorticoid receptor beta