title: Associations of HLA-DRB1 alleles with anti-citrullinated protein antibody-positive and anti-citrullinated protein antibody-negative rheumatoid arthritis in northern east part of Turkey.
abstract: OBJECTIVE
  The aim of this study was to investigate the associations between human leukocyte antigen (HLA)-DRB1 alleles with genetic susceptibility to rheumatoid arthritis (RA) and production of antibodies against cyclic citrullinated peptide (anti-CCP antibody) and rheumatoid factor (RF) in Turkish RA patients.
  
  
  METHODS
  We studied 291 RA patients and 253 controls. Genotyping was performed by polymerase chain reaction with sequence-specific oligonucleotide probes hybridization method. Serum levels of anti-CCP antibody, IgM-RF and high sensitive C-reactive protein titers were measured by commercial kits using immunological methods.
  
  
  RESULTS
  We found that HLA-DRB1*04 and *09 alleles were associated in anti-CCP+ and anti-CCP+ RA patients (P < 0.0001 and P < 0.001, respectively), while DRB1*01 and *04 were determined to be higher in RF+ RA patients (P < 0.001 and P < 0.0001, respectively). Moreover, DRB1*11 and DRB1*13 alleles were determined to be lower in RF and anti-CCP/RF+ RA patients (P < 0.001 for both). HLA-DRB1*04 was identified as a common responsible allele for susceptibility to the disease in anti-CCP, RF and anti-CCP/RF- RA patients (P = 0.0018, P = 0.0004 and P = 0.0023, respectively). HLA-DRB1*13 allele alone was found to be protective against to anti-CCP+ and RF- RA (P = 0.0003 and P = 0.006, respectively). On the contrary, there was no protective allele in anti-CCP/RF- RA as well as anti-CCP- RA patients.
  
  
  CONCLUSIONS
  This study indicates that associate and protective HLA-DRB1 allele distributions are different in autoantibody (anti-CCP or RF or anti-CCP/RF)+ RA and autoantibody- RA patients, with exceptions of DRB1*04 and DRB1*13.
authors.affiliation: Departments of Medical Biology & Genetics, Karadeniz Technical University, Trabzon, Turkey. fahriucar61@yahoo.com
authors.forename: Fahri
authors.initials: F
authors.lastname: Uçar
authors.forename: Erhan
authors.initials: E
authors.lastname: Çapkin
authors.forename: Murat
authors.initials: M
authors.lastname: Karkucak
authors.forename: Burcu
authors.initials: B
authors.lastname: Yücel
authors.forename: Mehmet
authors.initials: M
authors.lastname: Sönmez
authors.forename: Ahmet
authors.initials: A
authors.lastname: Alver
authors.forename: Neşe
authors.initials: N
authors.lastname: Kaklikkaya
authors.forename: Mehmet
authors.initials: M
authors.lastname: Tosun
authors.forename: Emel
authors.initials: E
authors.lastname: Alemdaroğlu
authors.forename: Mustafa
authors.initials: M
authors.lastname: Solak
mesh_terms: D000328:Adult; D000368:Aged; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000032:analysis; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D059811:HLA-DRB1 Chains / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D010456:Peptides, Cyclic / Q000276:immunology*; D010641:Phenotype; D012217:Rheumatoid Factor / Q000276:immunology; D014421:Turkey / Q000453:epidemiology
chemical_list: D001323:Autoantibodies; D015415:Biomarkers; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; C487763:cyclic citrullinated peptide; D002097:C-Reactive Protein; D012217:Rheumatoid Factor