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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-&#x03B1;). 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&#8211;3.73), P=2.0&#x00D7;10&#x2212;3]. This autoantibody profile was associated with higher serum IFN-&#x03B1; (P=7.6&#x00D7;10&#x2212;6). In the HapMap Yoruba population, rs3813065 was associated with differential expression of ERAP2 (P=2.0&#x00D7;10&#x2212;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

Promoter Variant ofPIK3C3Is Associated with Autoimmunity against Ro and Sm Epitopes in African-American Lupus Patients