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

Overview

Journal J Biomed Biotechnol

Specialty Biology

Date 2010 Jul 31

PMID 20671926

Citations 19

Authors

Silvia N Kariuki

Beverly S Franek

Rachel A Mikolaitis

Tammy O Utset

Meenakshi Jolly

Andrew D Skol

Timothy B Niewold

Affiliations

Soon will be listed here.

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-alpha). 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 x 10(-3)]. This autoantibody profile was associated with higher serum IFN-alpha (P = 7.6 x 10(-6)). In the HapMap Yoruba population, rs3813065 was associated with differential expression of ERAP2 (P = 2.0 x 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.

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