Promoter Variant of PIK3C3 Is Associated with Autoimmunity against Ro and Sm Epitopes in African-American Lupus Patients. (4th July 2010)

• Record Type: Journal Article
• Authors: Kariuki, Silvia N.; Franek, Beverly S.; Mikolaitis, Rachel A.; Utset, Tammy O.; Jolly, Meenakshi; Skol, Andrew D.; Niewold, Timothy B.
• Other Names: Poole Brian Academic Editor.
• Is Part Of: Journal of biomedicine and biotechnology. Volume 2010(2010)
• Publication Date: 2010-07-04
• Subjects: Medicine -- Periodicals; Biology -- Periodicals; Biotechnology -- Periodicals; Medicine; Biology; Biotechnology; Médecine; Biologie; Biotechnologie; Biology; Biotechnology; Medicine; Biotechnology; Biomedicine; Electronic journals; Periodical; Periodicals; Electronic journals; 610
• DOI: 10.1155/2010/826434
• Languages: English
• ISSNs: 1110-7243

Abstract

Abstract : 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.