Association of IL4R single-nucleotide polymorphisms with rheumatoid nodules in African Americans with rheumatoid arthritis.
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.
Burgos
Paula I
PI
University of Alabama, Tuscaloosa, Alabama 35487, USA.
Causey
Zenoria L
ZL
Tamhane
Ashutosh
A
Kelley
James M
JM
Brown
Elizabeth E
EE
Hughes
Laura B
LB
Danila
Maria I
MI
van Everdingen
Amalia
A
Conn
Doyt L
DL
Jonas
Beth L
BL
Callahan
Leigh F
LF
Smith
Edwin A
EA
Brasington
Richard D
RD
Moreland
Larry W
LW
van der Heijde
Désirée M
DM
Alarcón
Graciela S
GS
Bridges
S Louis
SL
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
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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