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Abstract Number: 1621

Genetic Contributions to Radiographic Damage in African Americans with Rheumatoid Arthritis on a Panel of Autoimmune Disease Markers

Vincent A. Laufer1, Richard J. Reynolds2, Peter K. Gregersen3, S. Louis Bridges Jr.4, Maria I. Danila5 and CLEAR Investigators, 1Division of Clinical Rheumatology and Immunology, University of Alabama at Birmingham, Birmingham, AL, 2Medicine, University of Alabama at Birmingham, Birmingham, AL, 3Robert S. Boas Center for Genomics and Human Genetics, Feinstein Institute for Med Res, Manhasset, NY, 4Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, AL, 5AL

Meeting: 2015 ACR/ARHP Annual Meeting

Date of first publication: September 29, 2015

Keywords: GWAS, Immunogenetics and rheumatoid arthritis, pathogenesis

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Session Information

Date: Monday, November 9, 2015

Title: Rheumatoid Arthritis - Human Etiology and Pathogenesis Poster II

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Rheumatoid arthritis (RA) is a complex autoimmune condition affecting 0.5-1% of populations worldwide and having a significant heritable component. A major endophenotype within RA is erosive joint damage, which is associated with autoantibodies and is manifested by bony erosions and joint space narrowing. In this study we seek to uncover influences on RA severity using the Immunochip custom array in order to both validate established loci of RA severity and discover novel contributing loci. 

Methods: Genotyping was performed on the Immunochip custom array, which was designed for the interrogation of autoimmune phenotypes. In addition, hand and foot radiographs from 548 African American RA patients were available for this study.  The total radiographic score ranged from 0 to 140, and we separated these patients into two groups, those having an erosion score of 0 (n=235) and those having an erosion score greater than 0 (n=313). After standard quality control measures for genotype missingness, Hardy-Weinberg equilibrium, etc., logistic regression was carried out while controlling for disease duration, proportion of European admixture, sex, Body Mass Index (BMI), smoking status, DMARD or Biologic use, and number of HLA-DRB1 risk alleles as covariates. We also fitted zero-inflated negative binomial models using total radiographic score as count data. We defined statistical significance at p=3.1*10-6based on an Neff of 16,154 calculated using Plink.

Results: rs1466576 reached Immunochip-wide statistical significance (OR=2.19, p = 1.81*10-6, nearest gene, PCBD1).  CTLA4 also showed suggestive evidence of association with radiographic severity, and the lead SNP was rs73055463, OR=0.39, p=1.47*10-5) in CTLA4, an established risk locus in rheumatoid arthritis. Finally, rs506746 (in NALCN, near ITGBL1) was associated with RA severity (p=9.93*10-7) using zero-inflated negative binomial model).  

Conclusion: This is the first study to evaluate the genetic contribution to radiographic severity in African Americans with RA. Using the Immunochip we found that PCBD1, NALCN/ITGBL1, and CTLA4 are associated with radiographic severity in African Americans with RA. These findings, while preliminary, may help extend knowledge of the genetic basis of radiographic damage in RA among African Americans, an understudied population in RA research.


Disclosure: V. A. Laufer, None; R. J. Reynolds, K01 NIH Research Grant, 2; P. K. Gregersen, None; S. L. Bridges Jr., None; M. I. Danila, None.

To cite this abstract in AMA style:

Laufer VA, Reynolds RJ, Gregersen PK, Bridges SL Jr., Danila MI. Genetic Contributions to Radiographic Damage in African Americans with Rheumatoid Arthritis on a Panel of Autoimmune Disease Markers [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/genetic-contributions-to-radiographic-damage-in-african-americans-with-rheumatoid-arthritis-on-a-panel-of-autoimmune-disease-markers/. Accessed .
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