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

Timothy B. Niewold, Silvia N. Kariuki, Beverly S. Franek, Rachel A. Mikolaitis, Tammy O. Utset, Meenakshi Jolly, Andrew D. Skol

Research output: Contribution to journalArticle

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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-). 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- (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.

Original languageEnglish (US)
Article number826434
JournalJournal of Biomedicine and Biotechnology
Volume2010
DOIs
StatePublished - 2010
Externally publishedYes

Fingerprint

Autoimmunity
African Americans
Systemic Lupus Erythematosus
Autoantibodies
Epitopes
Interferon-alpha
Genes
HapMap Project
Peptides
Genome-Wide Association Study
Enzymes
Processing
Serum
Anti-Idiotypic Antibodies
Antibodies
Population

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Genetics
  • Molecular Biology
  • Health, Toxicology and Mutagenesis
  • Medicine(all)

Cite this

Niewold, T. B., Kariuki, S. N., Franek, B. S., Mikolaitis, R. A., Utset, T. O., Jolly, M., & Skol, A. D. (2010). Promoter variant of PIK3C3 is associated with autoimmunity against Ro and Sm epitopes in African-American lupus patients. Journal of Biomedicine and Biotechnology, 2010, [826434]. https://doi.org/10.1155/2010/826434

Promoter variant of PIK3C3 is associated with autoimmunity against Ro and Sm epitopes in African-American lupus patients. / Niewold, Timothy B.; Kariuki, Silvia N.; Franek, Beverly S.; Mikolaitis, Rachel A.; Utset, Tammy O.; Jolly, Meenakshi; Skol, Andrew D.

In: Journal of Biomedicine and Biotechnology, Vol. 2010, 826434, 2010.

Research output: Contribution to journalArticle

Niewold, Timothy B. ; Kariuki, Silvia N. ; Franek, Beverly S. ; Mikolaitis, Rachel A. ; Utset, Tammy O. ; Jolly, Meenakshi ; Skol, Andrew D. / Promoter variant of PIK3C3 is associated with autoimmunity against Ro and Sm epitopes in African-American lupus patients. In: Journal of Biomedicine and Biotechnology. 2010 ; Vol. 2010.
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