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-). 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 10 -3 ]. This autoantibody profile was associated with higher serum IFN- (P=7.6 10 -6). In the HapMap Yoruba population, rs3813065 was associated with differential expression of ERAP2 (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.
ASJC Scopus subject areas
- Molecular Medicine
- Molecular Biology
- Health, Toxicology and Mutagenesis