Promoter Variant of PIK3C3 Is Associated with Autoimmunity against Ro and Sm Epitopes in African-American Lupus Patients

الملخص EN

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-α).

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-α (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.