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Eastern Regional Meeting - 2008 Program & Abstracts
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Single nucleotide polymporhisms in TNFAIP3, TRAF1/C5, and PTPN22 regions show association with Caucasian systemic lupus erythematosus but not with Korean rheumatoid arthritis
B.D. Korman, D. Kastner, E. Remmers, Genetics and Genomics Branch, National Institute of Arthritis Muskuloskeletal and Skin Diseases, Bethesda, MD; H. Lee, S. Bae, Department of Rheumatology, Hanyang University College of Medicine and the Hospital for Rheumatic Diseases, Seoul, SOUTH KOREA; H. Lee, P. Gregersen, Robert S Boas Center For Genetics & Genomics, Feinstein Institute for Biomedical Research, Manhassett, NY; L. Criswell, Department of Rheumatology, University of California San Francisco, San Francisco, CA; B.D. Korman, Clinical Research Training Program, National Institutes of Health, Bethesda, MD
Purpose of Study: Recent association studies of rheumatoid arthritis (RA) in Caucasian populations have identified multiple new disease-associated single nucleotide polymorhisms (SNPs). SNPs in the STAT4 gene were recently shown to be associated with both Caucasian SLE and Korean RA. We sought to determine whether SNPs in other regions associated with Caucasian RA were associated with either Caucasian systemic lupus erythematosus (SLE) or Korean RA.
Methods Used: DNA was collected from 1039 Caucasian SLE patients and 1248 Caucasian controls as well 1123 Korean RA patients and 1008 controls and analyzed for SNPs in the Caucasian RA associated genes TRAF1/C5, TNFAIP3, STAT4, PTPN22, IL2/21, CD40, AFF3, and CCL21 as well as the Asian RA associated genes PADI4, FCRL3, RUNX1, and SLC22A4. Because the Caucasian RA-associated SNP in PTPN22 is known to be monomorphic in Asians, tag SNPs covering the PTPN22 region were also assayed in Korean RA patients and controls.
Summary of Results: In addition to the previously reported STAT4 (p=6.9*10-9) and PTPN22 (p=1.6*10-5) SNPs, Caucasian SLE was strongly associated with SNPs in TRAF1/C5 (p=1.5*10-6) and TNFAIP3 (p=9.0*10-8) regions and moderately associated with a SNP near CCL21 (p=0.002). In contrast, Korean RA was associated with STAT4 (p=0.01), AFF3 (p=0.002) and strongly associated with PADI4 (p=1.1 * 10-8) but not associated with any of the other SNPs previously shown to be associated with RA including polymorphic variants covering the PTPN22 LD block.
Conclusions: While phenotypically similar, Caucasian RA and Korean RA seem to have different genetic risk factors. Conversely, Caucasian RA and SLE share multiple risk alleles.
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