Journal
JOURNAL OF BIOMEDICINE AND BIOTECHNOLOGY
Volume -, Issue -, Pages -Publisher
HINDAWI LTD
DOI: 10.1155/2010/826434
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Funding
- Genentech
- T. B. Niewold
- NIH [K08 AI083790]
- NIAID [AI071651]
- NIH CTSA
- CTSA [UL1 RR024999]
- Lupus Research Institute
- Alliance for Lupus Research Target Identification in Lupus Grant
- Arthritis National Research Foundation
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR024999] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [K08AI083790] Funding Source: NIH RePORTER
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The PIK3C3 locus was implicated in case-case genome-wide association study of systemic lupus erythematosus (SLE) which we had performed to detect genes associated with autoantibodies and serum interferon-alpha (IFN-alpha). Herein, we examine a PIK3C3 promoter variant (rs3813065/-442 C/T) in an independent multiancestral cohort of 478 SLE cases and 522 controls. rs3813065 C was strongly associated with the simultaneous presence of both anti-Ro and anti-Sm antibodies in African-American patients [OR - 2.24 (1.34-3.73), P - 2.0 x 10(-3)]. This autoantibody profile was associated with higher serum IFN-alpha (P - 7.6 x 10(-6)). In the HapMap Yoruba population, rs3813065 was associated with differential expression of ERAP2 (P = 2.0 x 10(-5)), which encodes an enzyme involved in MHC class I peptide processing. Thus, rs3813065 C is associated with a particular autoantibody profile and altered expression of an MHC peptide processing enzyme, suggesting that this variant modulates serologic autoimmunity in African-American SLE patients.
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