title: Promoter variant of PIK3C3 is associated with autoimmunity against Ro and Sm epitopes in African-American lupus patients.
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.
authors.affiliation: Section of Rheumatology and Gwen Knapp Center for Lupus and Immunology Research, University of Chicago, 5841 S. Maryland Ave. MC 0930, Chicago, IL 60637, USA.
authors.forename: Silvia N
authors.initials: SN
authors.lastname: Kariuki
authors.forename: Beverly S
authors.initials: BS
authors.lastname: Franek
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Mikolaitis
authors.forename: Tammy O
authors.initials: TO
authors.lastname: Utset
authors.forename: Meenakshi
authors.initials: M
authors.lastname: Jolly
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Skol
authors.forename: Timothy B
authors.initials: TB
authors.lastname: Niewold
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000483:Alleles; D000626:Aminopeptidases / Q000235:genetics / Q000378:metabolism; D000918:Antibody Specificity / Q000276:immunology; D001323:Autoantibodies / Q000276:immunology; D015551:Autoimmunity / Q000235:genetics*; D016022:Case-Control Studies; D058546:Class III Phosphatidylinositol 3-Kinases / Q000235:genetics*; D030541:Databases, Genetic; D000939:Epitopes / Q000276:immunology*; D005786:Gene Expression Regulation; D056426:Genetic Loci / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D016898:Interferon-alpha / Q000097:blood; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D025341:Principal Component Analysis; D011401:Promoter Regions, Genetic / Q000235:genetics*
chemical_list: D001323:Autoantibodies; D000939:Epitopes; D016898:Interferon-alpha; D019869:Phosphatidylinositol 3-Kinases; D058546:Class III Phosphatidylinositol 3-Kinases; D000626:Aminopeptidases; C503944:ERAP2 protein, human