Promoter variant of PIK3C3 is associated with autoimmunity against Ro and Sm epitopes in African-American lupus patients

J Biomed Biotechnol. 2010;2010:826434. doi: 10.1155/2010/826434. Epub 2010 Jul 4.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • African Americans / genetics*
  • Alleles
  • Aminopeptidases / genetics
  • Aminopeptidases / metabolism
  • Antibody Specificity / immunology
  • Autoantibodies / immunology
  • Autoimmunity / genetics*
  • Case-Control Studies
  • Class III Phosphatidylinositol 3-Kinases / genetics*
  • Databases, Genetic
  • Epitopes / immunology*
  • Gene Expression Regulation
  • Genetic Loci / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Interferon-alpha / blood
  • Lupus Erythematosus, Systemic / blood
  • Lupus Erythematosus, Systemic / enzymology
  • Lupus Erythematosus, Systemic / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Phosphatidylinositol 3-Kinases / genetics*
  • Polymorphism, Single Nucleotide / genetics*
  • Principal Component Analysis
  • Promoter Regions, Genetic / genetics*

Substances

  • Autoantibodies
  • Epitopes
  • Interferon-alpha
  • Phosphatidylinositol 3-Kinases
  • Class III Phosphatidylinositol 3-Kinases
  • Aminopeptidases
  • ERAP2 protein, human