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

Abstract

ThePIK3C3locus 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-α). Herein, we examine aPIK3C3promoter 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=2.0×10−3]. This autoantibody profile was associated with higher serum IFN-α(P=7.6×10−6). In the HapMap Yoruba population, rs3813065 was associated with differential expression ofERAP2(P=2.0×10−5), 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.