title: Association of IL4R single-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis.
abstract: BACKGROUND
  To determine whether IL4R single-nucleotide polymorphisms (SNPs) rs1805010 (I50V) and rs1801275 (Q551R), which have been associated with disease severity in rheumatoid arthritis (RA) patients of European ancestry, relate to the presence of rheumatoid nodules and radiographic erosions in African Americans.
  
  
  METHODS
  Two IL4R SNPs, rs1805010 and rs1801275, were genotyped in 749 patients from the Consortium for Longitudinal Evaluation of African-Americans with Early Rheumatoid Arthritis (CLEAR) registries. End points were rheumatoid nodules defined as present either by physical examination or by chest radiography and radiographic erosions (radiographs of hands/wrists and feet were scored using the modified Sharp/van der Heijde system). Statistical analyses were performed by using logistic regression modeling adjusted for confounding factors.
  
  
  RESULTS
  Of the 749 patients with RA, 156 (20.8%) had rheumatoid nodules, with a mean age of 47.0 years, 84.6% female gender, and median disease duration of 1.9 years. Of the 461 patients with available radiographic data, 185 (40.1%) had erosions (score>0); their mean age was 46.7 years; 83.3% were women; and median disease duration was 1.5 years. Patients positive for HLA-DRB1 shared epitope (SE) and autoantibodies (rheumatoid factor (RF) or anti-cyclic citrullinated peptide (CCP)) had a higher risk of developing rheumatoid nodules in the presence of the AA and AG alleles of rs1801275 (odds ratio (OR)adj=8.08 (95% confidence interval (CI): 1.60-40.89), P=0.01 and ORadj=2.97 (95% CI, 1.08 to 8.17), P=0.04, respectively). Likewise, patients positive for the HLA-DRB1 SE and RF alone had a higher risk of developing rheumatoid nodules in presence of the AA and AG alleles of rs1801275 (ORadj=8.45 (95% CI, 1.57 to 45.44), P=0.01, and ORadj=3.57 (95% CI, 1.18 to 10.76), P=0.02, respectively) and in the presence of AA allele of rs1805010 (ORadj=4.52 (95% CI, 1.20 to 17.03), P=0.03). No significant association was found between IL4R and radiographic erosions or disease susceptibility, although our statistical power was limited by relatively small numbers of cases and controls.
  
  
  CONCLUSIONS
  We found that IL4R SNPs, rs1801275 and rs1805010, are associated with rheumatoid nodules in autoantibody-positive African-American RA patients with at least one HLA-DRB1 allele encoding the SE. These findings highlight the need for analysis of genetic factors associated with clinical RA phenotypes in different racial/ethnic populations.
authors.affiliation: University of Alabama, Tuscaloosa, Alabama 35487, USA.
authors.forename: Paula I
authors.initials: PI
authors.lastname: Burgos
authors.forename: Zenoria L
authors.initials: ZL
authors.lastname: Causey
authors.forename: Ashutosh
authors.initials: A
authors.lastname: Tamhane
authors.forename: James M
authors.initials: JM
authors.lastname: Kelley
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Brown
authors.forename: Laura B
authors.initials: LB
authors.lastname: Hughes
authors.forename: Maria I
authors.initials: MI
authors.lastname: Danila
authors.forename: Amalia
authors.initials: A
authors.lastname: van Everdingen
authors.forename: Doyt L
authors.initials: DL
authors.lastname: Conn
authors.forename: Beth L
authors.initials: BL
authors.lastname: Jonas
authors.forename: Leigh F
authors.initials: LF
authors.lastname: Callahan
authors.forename: Edwin A
authors.initials: EA
authors.lastname: Smith
authors.forename: Richard D
authors.initials: RD
authors.lastname: Brasington
authors.forename: Larry W
authors.initials: LW
authors.lastname: Moreland
authors.forename: Désirée M
authors.initials: DM
authors.lastname: van der Heijde
authors.forename: Graciela S
authors.initials: GS
authors.lastname: Alarcón
authors.forename: S Louis
authors.initials: SL
authors.lastname: Bridges
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D000906:Antibodies / Q000097:blood; D001172:Arthritis, Rheumatoid / Q000208:ethnology* / Q000235:genetics*; D005260:Female; D005528:Foot / Q000000981:diagnostic imaging; D006684:HLA-DR Antigens / Q000097:blood; D059811:HLA-DRB1 Chains; D006225:Hand / Q000000981:diagnostic imaging; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D010456:Peptides, Cyclic / Q000276:immunology; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011859:Radiography; D019948:Receptors, Interleukin-4 / Q000235:genetics*; D012217:Rheumatoid Factor / Q000097:blood; D012218:Rheumatoid Nodule / Q000208:ethnology* / Q000235:genetics*; D012720:Severity of Illness Index
chemical_list: D000906:Antibodies; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010456:Peptides, Cyclic; D019948:Receptors, Interleukin-4; C487763:cyclic citrullinated peptide; D012217:Rheumatoid Factor
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