Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Genetic Associations with Serologic Autoimmunity in a Large Multi-Ancestral Systemic Lupus Erythematosus Cohort.

Kariuki1,  Silvia, Franek1,  Beverly S., Kumar1,  Akaash A., Kumabe1,  Marissa, Kaufman2,  Kenneth M., Anaya3,  Juan-Manuel, Alarcon-Riquelme4,  Marta E.

University of Chicago, Chicago, IL
Oklahoma Medical Research Foundation and Oklahoma University Health Sciences Center, Oklahoma City, OK
University of Alabama at Birmingham, Birmingham, AL
Instituto de Parasitologia y Biomedicina Lopez-Neyra (CSIC), Granada, Spain
Oklahoma Medical Research Foundation, Oklahoma City, OK
Sanatorio Parque, Rosario, Argentina
David Geffen School of Medicine University of California Los Angeles, Los Angeles, CA
Divisions of Genetics and Molecular Medicine and Immunology, King's College London, London, United Kingdom
Cincinnati Children's Hospital Medical Center and the US Department of Veterans Affairs Medical Center, Cincinnati, OH
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation, Oklahoma City, OK
Arthritis and Clinical Immunology Research Program, Oklahoma Medical Research Foundation and US Department of Veterans Affairs Medical Center, Oklahoma City, OK
Universidad del Rosario-Corporacion para Investigaciones Biologicas, Bogota, Colombia
Oklahoma Medical Research Foundation and Centro de Genómica e Investigación Oncológica Pfizer-Universidad de Granada-Junta de Andalucía (GENYO), Granada, Spain, on behalf of the BIOLUPUS and GENLES networ
Hanyang University Hospital for Rheumatic Diseases, Clinical Research Center for Rheumatoid Arthritis (CRCRA), Seoul, South Korea
Department of Medicine and Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL
Wake Forest School of Medicine, Winston-Salem, NC
Division of Rheumatologyand Immunology, Medical University of South Carolina, Charleston, SC
Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA

Background/Purpose:

Systemic lupus erythematosus (SLE) is a highly heterogeneous disorder characterized by production of autoantibodies directed at particular self-antigens in the cell nucleus. Similar to other autoimmune diseases, the genetic basis of SLE appears to vary in different serologic groups. We followed up loci from a case-only GWAS study which were associated with particular autoantibodies.

Methods:

We genotyped 43 tag SNPs from 10 regions identified in the above GWAS in a multi-ancestral SLE cohort of over 8000 patients split between African-American, European, Hispanic, and Asian ancestral backgrounds. For each SNP and by ethnic group, we computed admixture adjusted logistic regression analyses among cases for association between the SNPs and the presence or absence of the autoantibodies. P-values less than 1.2×10-3 withstand Bonferroni correction for the number of SNPs tested.

Results:

In African-Americans, the rs310230 SNP in JAK1 was strongly associated with anti-dsDNA and anti-RNP antibodies in an additive manner (OR=1.63, p=6.20×10-05). Additionally, a SNP in KLHL6 demonstrated evidence for association in the anti-RNP positive, anti-Sm negative group (p=2.1×10-3). In Asian ancestry, MAPK4 rs7242442 was associated with anti-Ro antibodies (OR=1.68, p=4.49×10-05). In Hispanic subjects, the strongest serologic association was also with the MAPK4 rs7242442 SNP, although it was associated with anti-RNP in this background (OR=1.47, p=3.9×10-3). In European ancestry, the strongest evidence for a SNP-antibody association was observed between a different MAPK4 tag SNP and anti-Ro antibodies (OR=1.23, p=5.3×10-3).

Conclusion:

We demonstrate association of SNPs within the JAK1, KLHL6, and MAPK4 genes with SLE-specific autoantibodies. Serologic autoimmunity differs greatly by ancestral background in SLE, and different autoantibodies have been associated with important clinical differences in patients. This study begins to genetically map this aspect of SLE across multiple ancestral backgrounds.

To cite this abstract, please use the following information:
Kariuki, Silvia, Franek, Beverly S., Kumar, Akaash A., Kumabe, Marissa, Kaufman, Kenneth M., Anaya, Juan-Manuel, et al; Genetic Associations with Serologic Autoimmunity in a Large Multi-Ancestral Systemic Lupus Erythematosus Cohort. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :633
DOI:

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